B cell or B lymphocytes – Definition, Function, Types

• The bursa of Fabricius, a lymphoid structure found near the tail end of the intestine in birds, plays a crucial role in the differentiation of B lymphocytes or B cells.
• A mammalian counterpart to the bursa has not yet been identified. In the bone marrow, the initial steps of development of these cells occur.
• B cells constitute nearly 30% of the recirculating small lymphocytes.
• The lifespan of B cells is measured in days or weeks. Approximately 109 B cells are created daily.
• The germinal centres of the lymph nodes, the white pulp of the spleen, and the MALT all contain B lymphocytes.
• B cells serve two essential tasks. First, they undergo plasma cell differentiation and antibody production. They can also present antigen to T helper cells.

What are B cells or B lymphocytes?

• B cells, commonly known as B lymphocytes, are a type of lymphocyte subtype white blood cell.
• They function in the adaptive immune system’s humoral immunity component. B cells generate antibody molecules that can be released or inserted into the plasma membrane, where they function as B-cell receptors.
• When a naive or memory B cell is activated by an antigen, it proliferates and develops into a plasmablast or plasma cell, which is an antibody-secreting effector cell.
• In addition to presenting antigens and secreting cytokines, B cells are classed as professional antigen-presenting cells (APCs).
• B cells mature in the bone marrow, which is located near the centre of most bones in mammals. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ where Chang and Glick initially discovered them; therefore, the ‘B’ does not stand for bone marrow as is usually assumed.
• B cells express B cell receptors (BCRs) on their cell membrane, in contrast to T cells and natural killer cells. BCRs enable the B cell to bind to an alien antigen, against which it will launch an antibody response.

B lymphocytes Cells Morphology

B lymphocytes Cells under Light Microscopy

• In general, histochemistry and flow cytometry are the most effective methods for differentiating lymphocyte types; the light microscope cannot discriminate cell types purely on appearance.
• On glass slides, however, light microscopy reveals lymphocytes to be spherical or ovoid cells with sizes ranging from 6 to 15 μm.
• Lymphocyte sample preparation often involves air-dried film staining with Romanowsky polychromatic stains (e.g., Giemsa or Wright).
• The light microscope reveals two groups of lymphocytes: (1) giant cells with 9 to 15 μm diameters and (2) tiny lymphocytes with 6 to 9 μm diameters.
• Under a microscope, lymphocytes appear as dark purple cells with a deep blues nucleus and pale azure cytoplasm. Due to the substantial amount of condensed chromatin, nuclei occupy a significant fraction of the cellular interior.

B lymphocytes Cells under Electron Microscopy

Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) can be used to examine B cells (TEM). However, each technique depicts b cells from a unique angle. TEM permits us to examine the interior of cells. However, SEC reveals the surface outside of B lymphocytes.

Transmission Electron Microscopy

• Under transmission electron microscopy, the blood lymphocyte nucleus displays electron-dense heterochromatin, a characteristic of non-dividing cells. The nucleoli of lymphocytes are round in section.
• Lymphocytes are organised into three concentric zones or structural units. (1) the central region (the Agranular zone), (2) the intermediate region (the fibrillar region), and (3) the outer region (the granular zone), which is made of intranuclear chromatin. Furthermore, The cytoplasmic organelles of lymphocytes are typical of eukaryotic cells.

Scanning Electron Microscopy

• This modality gives information in three dimensions. Nevertheless, it produces images with a lower resolution than transmission electron microscopy.
• Lymphocytes from normal blood that have been cleaned, collected on silver membranes, and preserved with glutaraldehyde.
• B cells under SEM range in diameter from 5.1 to 6.4 μm. B cells were distinguished by their intricate surface architecture, which consisted of numerous microvilli resembling fingers and covered their whole surface.

Origin of B cells

• The genesis of antibody production is explained by the hypothesis of clonal selection. According to this hypothesis, each immunologically competent B cell includes a receptor for either IgM or IgD that can combine with a single antigen or antigens that are closely related.
• Following antigen binding, the B cell is stimulated to grow and generate a clone. Certain B cells are converted into plasma cells that produce antigen-specific antibodies.
• Plasma cells produce immunoglobulins with the same antigenic specificity as B cells that have been activated. T cells experience the same clonal selection.
• During development, B cell precursors first multiply and grow in the foetal liver. From there, they travel to the bone marrow, the primary maturation destination for adult B-cells.
• They do not require the thymus for maturation, unlike T cells. Only heavy chains are present in the cytoplasm of Pre-B cells, which lack surface immunoglobulins and light chains.
• Pre-B cells are located in the bone marrow, whereas B cells are located in the bloodstream. B cells mature in two phases:
  • The antigen-independent phase, which comprises of stem cells and pre-B cells, and the antigen-dependent phase.
  • Antigen-dependent phase, which consists of activated B cells and plasma cells that proliferate in response to antigen-B cell interactions.
• B cells have surface IgM, which functions as an antigen receptor. Some B lymphocytes may also carry IgD on their surface as an antigen receptor.
• On the surface of B cells are expressed numerous other molecules with various roles. Among them are B220, molecules of class II MHC, CR1 and CR2, CD40, and others.

Effector functions of B cells

• Activation of B cells results in the production of many plasma cells. The plasma cells then create an abundance of immunoglobulins specific to the antigen’s epitope.
• Some activated B cells generate memory cells that persist in a quiescent state for months or years.
• Surface IgG serves as the antigen receptor on the majority of memory B cells, but some also express surface IgM.
• These latent memory cells are rapidly triggered upon antigen reexposure. Memory T cells generate interleukins that enhance memory B cell antibody synthesis.
• These cells are responsible for the fast emergence of antibodies during secondary immune reactions.

Types of B cell or B lymphocyte

1. Plasmablast

• A short-lived, proliferating antibody-secreting cell that results from the differentiation of B cells.
• Plasmablasts are formed early in an infection, and their antibodies have a lower affinity for their target antigen than plasma cell antibodies.
• Plasmablasts can develop through T cell-independent stimulation of B cells or from T cell-dependent activation of B cells resulting in an extrafollicular response.

2. Plasma cell

• Long-lived, non-proliferating, antibody-secreting B cell derivative. There is evidence that B cells first differentiate into cells resembling plasmablasts and later become plasma cells.
• Plasma cells are formed later in an infection and, as a result of affinity maturation in the germinal centre (GC), have antibodies with a stronger affinity for their target antigen than plasmablasts and produce more antibodies.
• Plasma cells are often the product of the germinal centre response resulting from T cell-dependent activation of B cells, but they can also be the result of T cell-independent activation of B cells.

3. Lymphoplasmacytoid cell

• A cell exhibiting morphological characteristics of both B lymphocytes and plasma cells, believed to be closely related to or a subtype of plasma cells.
• These dyscrasias include IgM monoclonal gammopathy of unknown relevance and Waldenstrom’s macroglobulinemia.

4. Memory B cell

• A dormant B cell is the result of B cell differentiation. If they recognise the antigen that stimulated their parent B cell, they circulate throughout the body and initiate a stronger, more faster antibody response (known as the anamnestic secondary antibody response) (memory B cells and their parent B cells share the same BCR, thus they detect the same antigen).
• Memory B cells can be created through T cell-dependent activation of B1 cells via the extrafollicular response and germinal centre reaction, as well as T cell-independent activation of B1 cells.

5. B-2 cell

FO B cells and MZ B cells.

a. Follicular (FO) B cell (also known as a B-2 cell)

• When not circulating in the blood, the most common kind of B cell is mostly located in the lymphoid follicles of secondary lymphoid organs (SLOs).
• During an infection, they are responsible for producing the majority of high-affinity antibodies.

b. Marginal-zone (MZ) B cell

• As the marginal zone of the spleen receives a substantial amount of blood from the general circulation, it serves as the first line of defence against blood-borne viruses.
• Both T cell-independent and T cell-dependent activation are possible, but T cell-independent activation is preferred.

6. B-1 cell

• Develops via a distinct developmental mechanism from FO B cells and MZ B cells.
• They occupy the peritoneal cavity and pleural cavity of mice, create natural antibodies (antibodies produced without infection), protect against mucosal pathogens, and demonstrate T cell-independent activation mostly.
• On humans, a real homologue of mouse B-1 cells has not been identified; rather, numerous B-1-like cell types have been characterised.

7. Regulatory B (Breg) cell

• A type of immunosuppressive B cell that inhibits the proliferation of pathogenic, pro-inflammatory lymphocytes by secreting IL-10, IL-35, and TGF-β.
• Additionally, it increases the production of regulatory T (Treg) cells by directly influencing the development of T cells towards Tregs.
• There has been no description of a common Breg cell identity, and several Breg cell subsets with similar regulatory roles have been identified in both mice and humans.
• It is still uncertain if Breg cell subgroups are developmentally connected and how Breg cells differentiate.
• There is evidence that practically all types of B cells are capable of differentiating into Breg cells via pathways involving inflammatory signals and BCR recognition.

Generation of B Cells

• The immune system is exceptional for its ability to respond to a large number of antigens, including recently produced molecules that did not previously exist.
• Antibody diversity is characterised by the inclusion of variable and constant sections on the same polypeptide chain and the utilisation of identical V regions with distinct C regions.
• The use of somatic recombination to generate antibody and TCR diversity is exclusive to mammalian genes. The successful synthesis of both the H and L chains, as well as their expression on the cell membrane, are required for the formation of B cells and serve as markers for the stages of this development.
• B cell formation begins in the foetal liver and continues throughout life in the bone marrow. The following table depicts the stages of B cell development. Once a B cell is able to express both the m and L chains on its membrane, it is considered to be a B cell.
• Until it expresses membrane IgD, however, it is still immature and can be easily destroyed by contact with self antigen. The mature B cell that migrates to the periphery can be triggered by antigen to become an antibody-secreting plasma cell or a memory B cell that responds more rapidly to a second antigen exposure.
• Apoptosis occurs in B cells that fail to successfully complete B cell development (programmed cell death).
• B cell development begins when lymphoid progenitor cells receive signals from bone marrow stromal cells. CD34+ lymphoid progenitors produce TdT and recombinases (RAG-1 and RAG-2) in response to cytokines.
• To become early pro-B cells, the cells undergo D-J joining on the H chain chromosome and begin expressing CD45 (B220) and Class II MHC. The late pro-B cell stage is concluded when a V segment joins the D-JH.
• When pro-B cells express membrane m chains with surrogate light chains in the pre-B receptor, they transform into pre-B cells. Surrogate L chains resemble authentic L chains, but are identical on each pre-B cell.
• Iga and Igb, signal transduction molecules, are also a component of the pre-B receptor complex. Ig heavy chain cytoplasmic tails are too short to enter the cytoplasm and send an antigen-binding signal; Ig an Ig b signal transduction molecules contain ITAMs (Immunoreceptor Tyrosine Activation Motifs) that are phosphorylated in response to antigen-BCR contact.
• The phosphorylation triggers a signalling cascade in the cytoplasm. The cell ceases H chain recombination and proliferates into clones of B cells that all produce the same m chain. Due to the fact that dividing cells are larger than resting cells, this stage is referred to as the giant pre-B cell.
• Following division, tiny pre-B cells undergo V-J chromosomal joining on one L chain chromosome. Once L chain has been made successfully, it is co-expressed with m chain on the cell membrane, at which point the cell is referred to as an immature B cell.
• If immature B cells adhere to their own antigen in the bone marrow, they will perish. B cells that do not bind self antigen express d chain and membrane IgD along with IgM as they exit the bone marrow and mature into naive (resting) B cells.

Regulation of B Cell Development

• Cell-cell interactions and released signals allow bone marrow stromal cells to communicate with progenitor cells. This microenvironment in bone marrow is responsible for B cell development.
• One set of CAMs implicated in the formation of both B and T cells consists of SCF (stem cell factor) on the membrane of stromal cells and kit (CD117) on the membrane of lymphocytes.
• IL-7, which is released by stromal cells and binds to IL-7R on growing lymphocytes, is a crucial cytokine for the development of both B and T cells.
• Signals from these binding events start cytoplasmic cascades that affect the expression of developmentally essential proteins.
• As the B cells mature in the bone marrow, they migrate from the exterior to the interior.
• In the growing B cell, somatic recombination can be either productive (resulting in the synthesis of a functioning H or L chain) or nonproductive due to the inclusion of a stop codon due to frame shift mutations.
• Failure to make productive rearrangements and express Ig at the proper moments during development leads to cell death. B cells have two opportunities to rearrange H chain (maternal and paternal chromosomes) and four opportunities to rearrange L chain (maternal and paternal chromosomes) (paternal and maternal k and l loci).
• Typically, human B cells rearrange DH and JH regions on both chromosomes concurrently. Additionally, DH can be read in any reading frame, making all D-J rearrangements productive.
• Only around half of growing B cells, according to estimates, undergo productive H chain rearrangements. These successful pre-B cells proliferate to produce B cell clones (the big pre-B cell stage), which are capable of L chain recombination.
• During the tiny pre-B cell stage, the V-J joining of the light chain often happens first for the k chain. If the rearrangement is successful, the k chain is produced and the cell develops into an immature B cell that expresses membrane IgM(k) BCR.
• B cells can retry V-J joining multiple times if the initial attempts fail; this mechanism is known as light chain rescue.
• l genes are rearranged if k genes cannot be successfully rearranged on either chromosome. Successful outcomes result in the formation of IgM(l) BCR. If neither k nor l is productively altered, the bone marrow cell undergoes apoptosis. A fraction of human pre-B cells do not develop into B cells.
• During B cell growth, genes producing proteins necessary for somatic recombination and receptor expression are turned on and off at predetermined intervals. RAG-1, RAG-2, and TdT are exclusively expressed during the early and late pro-B cell and tiny pre-B cell stages, when somatic recombination occurs.
• TdT is frequently turned off before recombinases, hence N nucleotide additions to gene segment join in L chain sequences are less frequent than in H chain sequences. The surrogate L chain, as well as the Ig a and Ig b chains, must be expressed in order for the pre-B receptor to emerge on the cell membrane.
• Signal transduction molecules must be expressed at critical moments; inability to express btk results in Bruton’s X-linked agammaglobulinemia, a human B cell immunodeficiency.
• The regulation of gene expression is dependent on soluble transcription factors that bind to DNA regulatory regions. Promoters are DNA sequences that bind RNA polymerase to trigger the synthesis of messenger RNA (mRNA).
• Enhancers are additional non-coding (intron) DNA sequences that boost the activity of promoters. Splicing of gene segments with looping out of intervening DNA brings promoters and enhancers closer together, thereby increasing the manufacture of messenger RNA (mRNA).
• Also required are tissue-specific enhancers, such as RAG-1 and RAG-2, which recombine only Ig gene segments in developing B cells and only TCR gene segments in developing T cells.

Positive Selection of B Cells

• In the primary lymphoid organs, B and T lymphocytes are both subject to positive and negative selection. Positive selection necessitates antigen receptor-mediated signalling for cell survival.
• The positive selection of developing B cells occurs when the pre-B receptor binds its ligand. (Developing T lymphocytes are favourably chosen on the basis of their ability to bind MHC and peptide.)
• Negative selection indicates that receptor binding results in cell death. If immature B and T cells bind self antigen, they are both negatively selected.
• Membrane pre-B receptor and membrane IgM expression transmit signals necessary for B cell survival and progression through the correct phases of gene expression. Two types of experiments have offered evidence for this claim.
• The H and L chains can be rearranged and then introduced into fertilised mouse eggs to produce transgenic mice. Mice transgenic for both recombined Ig H and L chains do not often recombine other Ig genes; all of their B cells express the transgene H and L chains.
• Transgenic mice for the H chain continue to recombine their genes for the L chain and vice versa. Therefore, the presence of an altered VH or VL gene communicates to the B cell to inhibit further recombination of that gene.
• Knock-out mice are mice in which functional genes (or portions of genes needed for their function) have been removed.
• Experiments demonstrating the importance of membrane expression of the BCR complex for delivering these signals involved creating mice lacking the H chain transmembrane exon (so that the H chain would not be inserted into the membrane), the genes for Iga or Igb (or just their ITAMs), or the genes for the surrogate light chains l5 and VpreB.
• Even if all other proteins can be produced or the complete pre-B receptor can be expressed on the membrane with the IgaIgb missing ITAMs, the elimination of any one of these proteins prevents the formation of B cells.
• Surrogate light chain l5 resembles the constant section of the l chain, but is encoded by a distinct gene. l5 forms a non-covalent association with a VpreB domain that mimics an Ig V domain.
• Since pre-B cells display several VH sections, it is theorised that the VpreB shared by all pre-B cells binds a ligand that tells the pre-B cell to divide and subsequently initiate light chain recombination via the signal transduction protein IgaIgb. Similar signals from unidentified ligands inhibit recombination.
• Somatic recombination results in allelic exclusion for both H and L chains in individual B cells, as only one H chain gene and one L chain gene are productively recombined in each B cell.
• In a heterozygote, each allele (allotype) is present on around fifty percent of B cells and fifty percent of serum Ig molecules. Light chains also exhibit isotypic exclusion, as a single cell or molecule contains either k or l chains. k and l are not equally represented on B cells and serum Igs. k is favoured over l by 65% to 35% in humans.
• In mice, 95% of the serum Ig is k, while in cats it is l. The ratio of k to l represents the proportional quantity of V region segments in each isotype and their recombination efficiency into functional L chain genes.
• Once a B cell leaves the bone marrow, its survival is believed to be dependent on additional signals supplied by lymphoid follicles of secondary lymphoid tissue.
• B cell homeostasis is likely maintained by the competition between newly generated and older B cells for these signals.
• It has been demonstrated that the survival of injected transgenic B cells (whose unique receptor can be recognised by flow cytometry) depends on the irradiation of the host’s regular B cells.

Negative Selection of B Cells

• B cells that express only IgM are destroyed or inactivated (negatively selected) when they bind multivalent ligands, in contrast to mature B cells that are activated by BCR cross-linking.
• In the bone marrow, binding to multivalent (cell-associated) self induces B cell death and clonal deletion. Binding to soluble self does not kill the B cell; the cell is able to migrate to the periphery and express mainly IgD and very little IgM.
• These cells lack the ability to respond to antigen and have a short lifespan. Non-self-binding cells express normal amounts of IgM and IgD; if they reach lymphoid follicles, they can live for a few weeks until they encounter their particular antigen or perish.
• Although many self-specific B cells undergo clonal deletion, others can undergo further somatic recombination to generate non-self-specific VH and VL combinations.
• Mice bearing Ig transgenes expressing self-MHC-specific BCR have showed that receptor editing can change the specificity of some self-specific B cells, thereby rescuing them.
• The few B lymphocytes produced by these mice are not self-specific, as they are capable of producing new (non-transgenic) recombinations. The V sections of both the light and heavy chains can be replaced during receptor modification.
• In numerous animal taxa, Ig germline diversity is absent or extremely low. Only one or a few functional V, D, and J segments are available for recombination, ensuring that all immature B cells have the same antigen specificity and bind self antigen.
• During cell division, DNA crossing over events with nearby pseudogenes (gene segments containing stop codons) cause modifications to the V region sequences.
• This technique generates several Ig V regions. Once cells cease to connect to themselves, they develop and migrate to the periphery.

Heterogeneity of B Cell

• During foetal development, bone marrow stem cells generate the B-1 B cell, a B cell with characteristics distinct from those of typical B cells. B-1 Cells have membrane CD5.
• They are self-renewing, meaning that they can make additional adult naïve cells similar to themselves by division in the lymphoid tissues of the periphery.
• Conventional B-2 cells can only divide in response to antigen and form memory or plasma cells in the periphery; bone marrow progenitors must be used to generate new naive B-2 cells.
• B-1 BCR is significantly less varied than B-2 BCR. B-1 BCR is generated preferentially from a subset of Ig gene segments, lacks extra N nucleotides at segment junctions, and is mostly selective for common bacterial carbohydrate antigens.
• B-1 cells largely produce IgM and experience minimal somatic hypermutation. B-1 cells and their produced antibodies are termed polyreactive because they respond to antigens found on numerous pathogens and bind various antigens with low affinity.
• B-1 cells produce the majority of the IgM observed in unvaccinated mice. B-1 cells produced after birth contain a greater diversity of Ig than those produced during foetal development, but not as much as B-2 cells.
• Eventually, stem cells in bone marrow cease making B-1 cells. The gamma/delta T cell is an early-developing T cell type that is similar to the gamma/delta T cell.
• B cells alter their location in accordance with their maturation stages, with each site providing a microenvironment optimal for the B cell at that point of its life. Just under the bone, stem cells generate lymphoid progenitors and pro-B cells in the bone marrow.
• As B cells mature, they migrate toward the core of the bone marrow. Mature naive B cells exit the bone marrow and use selectins to bind addressins on the endothelium of blood vessels to enter peripheral lymphoid tissues, passing via T cell areas and entering B cell areas (follicles).
• Peyer’s patches, tonsils, and the appendix consist primarily of enormous follicles. The milieu in the MALT follicles (including the T cell cytokines produced there) instructs the B cells to generate IgA, whereas the microenvironment in the lymph nodes and spleen instructs the B cells to manufacture IgG.
• B cells that contact antigen and receive the proper T cell assistance in the T cell regions develop germinal centres in the follicles, where they rapidly divide, undergo somatic hypermutation, and are selected for B cells with greater affinity receptors.
• Antibody-secreting plasma cells are largely present in the medullary cords of the lymph nodes, the red pulp of the spleen, the bone marrow (particularly IgG-secreting plasma cells), and the mucosal lamina propria (IgA-secreting plasma cells).
• Memory B cells are mostly present in the border zone of the spleen, the sub-capsular sinus of the lymph nodes, and under the intestinal epithelium in the Peyer’s patches and crypt epithelium of the tonsils; a small number are also detected in the blood.
• These spontaneously occurring malignancies have assisted immunologists in comprehending B cell development.
• Each form of tumour has its own unique Ig gene recombination status and homing characteristics. In nearly every instance, these tumours arise from a single B cell transformed into a cancer cell.
• Monoclonality permits clinicians to identify tumour cells and monitor their treatment responses.
• Some B cell malignancies contain DNA translocations that result in the activation of oncogenes. A translocation is the transfer of a section of one chromosome to another.
• Oncogenes are genes often linked with regulated cell division; disruption of their function by translocation can lead to uncontrolled proliferation.
• In Africa, Epstein Barr Virus (EBV), which often causes a benign childhood sickness or a more serious infectious mononucleosis in young people in the United States, is linked to Burkitt’s lymphoma, a type of B cell malignancy.
• Myc is translocated in Burkitt’s lymphoma cells under the direction of a H or L chain promoter. Because these promoters are active in B cells, a B cell with this translocation and additional mutations may experience uncontrolled proliferation.
• There appears to be a connection between Burkitt’s lymphoma and malaria. bcl-2 is another gene that is activated by translocation to Ig locus.
• Bcl-2 protein shields B-lineage cells from programmed cell death; therefore, cells containing translocated bcl-2 live beyond their natural lifespan and may develop cancer.

B-cell Activation

Activation of a B cell by a protein antigen requires the B cell to operate as an APC, presenting the protein epitopes on MHC II to helper T cells; therefore, this mechanism is referred to as T- cell-dependent activation. However, polysaccharides, lipopolysaccharides, and other non-protein antigens are termed T-independent antigens due to their ability to activate B cells without antigen processing and presentation to T cells.

T Cell-independent activation of B cells

• This sort of activation occurs when B cells engage with T-independent antigens; it is a two-signal activation process.
• Cross-linking of several BCRS with repeating epitope units on the surface of the antigen is the first signal.
• The interaction of toll-like receptors with PAMPs or interactions with complement factors is the second signal.
• Following B cell activation, B cells undergo clonal growth and ultimately plasma cell differentiation.
• B-cell receptors will eventually disappear. However, plasma cells with the same specificity as BCRs will dominate IgM antibody synthesis (Pentameric IgM). This mechanism is short-lived and inhibits the development of memory cells.

T Cell-Dependent Activation of B cells

• This process occurs as a result of T-dependent antigens (protein material either free or associated with intact pathogens).
• Interaction with free antigen will instantly result in internalisation. However, interaction with intact pathogens will lead to the separation and extraction of antigens from the intact pathogen.
• Antigen will eventually be displayed on MHC class 2 on the exterior membrane of B-cells, which will be recognised by T helper cells specific to that antigen.
• There will be linked recognition between T helper cells and B cells, which is explained by the TCR of T helper cells recognising the antigen presented on b cells and the CD4 molecule interacting with MHC-II on B cells.
• TH2 cells release several cytokines that encourage B cell proliferation and differentiation into plasma cells and memory cells.

Memory B cell activation

• Memory B cell activation begins with the identification and binding of their shared parent B cell’s target antigen.
• Certain memory B cells, such as virus-specific memory B cells, can be triggered without the assistance of T cells, but others require T cell assistance. Upon antigen binding, the memory B cell picks up the antigen via receptor-mediated endocytosis, destroys it, and offers it to T cells as peptide fragments bound to MHC-II molecules on the cell membrane.
• Through their TCR, memory T helper (TH) cells, often memory follicular T helper (TFH) cells, produced from T cells stimulated with the same antigen identify and bind these MHC-II-peptide complexes.
• Following TCR-MHC-II-peptide binding and the transmission of other signals from the memory TFH cell, the memory B cell is activated and either differentiates into plasmablasts and plasma cells via an extrafollicular response or enters a germinal centre reaction in which it generates plasma cells and additional memory B cells.
• It is unknown if memory B cells undergo additional affinity maturation in these secondary GCs.
• Memory B cells can be activated in vitro through stimulation with several activators, such as pokeweed mitogen or anti-CD40 monoclonal antibodies; however, according to a study, the most effective activator is a combination of R-848 and recombinant human IL-2.

B cell responses to antigen

• Mature FO In quest of antigen, B cells travel between secondary lymphoid organs. Upon encountering a cognate antigen, B cells aided by T cells may undergo a variety of developmental pathways.
• First, the cells are capable of plasmacytic differentiation, the formation of extrafollicular plasmablasts, and the formation of IgM-secreting plasma cells.
• These cells lack somatic mutations in their Ig genes and have a short lifespan, yet they offer a quick first response to antigen.
• The second developmental possibility is the formation of a germinal centre, a specialised structure in which B cells undergo cycles of proliferation accompanied by affinity maturation: an iterative process of Ig gene mutation and selection that results in a B cell pool with the highest affinity for antigen binding.
• In addition, the cells undergo class-switch recombination. Immunoglobulin class switching to IgG, IgA, and IgE is a significant mechanism for diversifying B cell responses and adapting antibody function to immunological stress.
• Exiting the GC are memory B cells and plasma cells bearing somatically altered and generally high affinity BCRs of switched isotypes.

Applications of B cell or B lymphocyte

• B cells serve as professional antigen-presenting cells in addition to their core function of antibody-mediated immune response.
• B lymphocytes are known to produce cytokines, which are crucial for cell-cell communication, particularly during an immunological response.
• The creation of antibodies is the most significant activity of B cells, which are engaged in the humoral immune response mediated by antibodies.
• B cells contribute to immunological control via cytokine synthesis and antigen presentation in addition to producing antibodies. Over the years, the use of B cells as APCs has expanded because they can be generated regularly from peripheral blood and are largely resistant to tumor-derived immunosuppressive mechanisms. In addition, these do not induce tolerance and are well tolerated in terms of harmful side effects.

References

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