Biology of the B Lymphocyte

B lymphocytes, or B cells, are a type of white blood cell that plays a key role in the adaptive immune system. They are responsible for producing antibodies, which are proteins that bind to specific antigens and help eliminate them from the body. B cells also function as antigen-presenting cells, which means they can display fragments of antigens on their surface and activate helper T cells, another type of immune cell that provides signals and support for B cells and other immune cells.

B cells are named after the bursa of Fabricius, an organ in birds that is essential for their antibody production. In mammals, however, B cells do not originate from the bursa, but from the bone marrow. The bone marrow is a soft tissue inside the bones that contains stem cells, which are immature cells that can differentiate into various types of blood cells. One of these types is the lymphoid stem cell, which gives rise to both B cells and T cells.

The differentiation of B cells from lymphoid stem cells involves several stages and molecular events that occur in the bone marrow and in other secondary lymphoid organs, such as the spleen and the lymph nodes. These stages and events ensure that B cells develop properly and acquire the ability to recognize a diverse range of antigens without reacting to self-antigens, which are molecules that belong to the body and should not trigger an immune response. The development of B cells also prepares them for activation by antigens and subsequent differentiation into antibody-secreting plasma cells or memory B cells, which can provide long-lasting immunity against repeated infections.

In this article, we will explore the biology of B cells in more detail, focusing on their differentiation, development, activation, and function in the immune system. We will also discuss some of the molecules and mechanisms that regulate B-cell responses and how they contribute to immunity and immunological disorders.

B cells are the lymphocytes that produce antibodies to fight infections. They develop from hematopoietic stem cells in the bone marrow, where they undergo a series of gene rearrangements and selection processes to generate a diverse repertoire of antigen receptors. The antigen receptors, also known as immunoglobulins (Ig) or B-cell receptors (BCR), consist of two heavy chains and two light chains that form a Y-shaped molecule. The variable regions of the heavy and light chains determine the specificity of the BCR for a particular antigen, while the constant regions determine the isotype and effector functions of the antibody.

The early stages of B-cell differentiation in the bone marrow can be divided into four main phases: pro-B, pre-B, immature B, and mature B. Each phase is characterized by the expression of different CD molecules on the cell surface and the status of Ig gene rearrangement.

• Pro-B cells are the earliest identifiable cells in the B-cell lineage. They express CD34, CD10, CD19, and CD127 on their surface. They initiate Ig heavy chain gene rearrangement by joining a diversity (D) segment to a joining (J) segment (D-J recombination), followed by joining a variable (V) segment to the D-J unit (V-D-J recombination). This process is mediated by enzymes called RAG1 and RAG2 and results in a functional heavy chain gene that can be transcribed and translated into a μ chain.
• Pre-B cells are the next stage of differentiation. They express CD10, CD19, CD20, and CD34 on their surface. They have completed heavy chain gene rearrangement and express a μ chain on their surface in association with surrogate light chains (λ5 and VpreB) and signal transduction molecules (Igα and Igβ). This complex is called the pre-BCR and signals the cell to stop further heavy chain gene rearrangement and to proliferate.
• Immature B cells are the stage after pre-B cells. They express CD10, CD19, CD20, and IgM on their surface. They have initiated light chain gene rearrangement by joining a V segment to a J segment (V-J recombination) for either κ or λ chains. This process is also mediated by RAG1 and RAG2 and results in a functional light chain gene that can be paired with the μ chain to form a complete IgM molecule. The IgM molecule is then expressed on the cell surface as part of the BCR complex with Igα and Igβ.
• Mature B cells are the final stage of differentiation in the bone marrow. They express CD19, CD20, CD21, CD23, IgM, and IgD on their surface. They have completed light chain gene rearrangement and express both IgM and IgD with identical antigen specificity on their cell surface. The expression of IgD is achieved by alternative splicing of the primary transcript of the heavy chain gene.

During B-cell differentiation in the bone marrow, some cells may generate BCRs that recognize self-antigens. These cells are eliminated by apoptosis or undergo receptor editing to avoid autoimmunity. Receptor editing is a process by which light chain gene rearrangement is reactivated and a new light chain is generated that may not bind to self-antigens. If receptor editing fails to produce a non-self-reactive BCR, the cell undergoes apoptosis.

Mature B cells exit the bone marrow and migrate to secondary lymphoid organs such as spleen, lymph nodes, tonsils, and mucosa-associated lymphoid tissue (MALT). There they encounter antigens and undergo further activation, proliferation, differentiation, and diversification into plasma cells or memory cells. Plasma cells are antibody-secreting cells that reside mainly in the bone marrow or MALT. Memory cells are long-lived cells that can rapidly respond to subsequent exposures to the same antigen.

The activation of mature B cells by antigens depends on whether the antigens are thymus-dependent (TD) or thymus-independent (TI). TD antigens are protein antigens that require T-cell help to induce B-cell responses. TI antigens are non-protein antigens such as polysaccharides or lipopolysaccharides that can activate B cells without T-cell help. The activation of B cells by TD antigens occurs mainly in germinal centers within secondary lymphoid organs. Germinal centers are specialized sites where B cells undergo somatic hypermutation (SHM) and class switch recombination (CSR). SHM introduces point mutations into the variable regions of Ig genes to increase their affinity for antigens. CSR changes the constant region of the heavy chain gene to switch the antibody isotype from IgM or IgD to IgG, IgA, or IgE, while retaining the same antigen specificity. The isotype switch is influenced by cytokines produced by T cells or other cells. Germinal center B cells that have high-affinity BCRs and receive adequate T-cell help survive and differentiate into memory B cells or plasma cells. Germinal center B cells that have low-affinity BCRs or fail to receive T-cell help undergo apoptosis.

The activation of B cells by TI antigens occurs mainly in the marginal zone of the spleen or in MALT. These antigens activate a subset of B cells called marginal zone B cells or B-1 cells, respectively. These B cells produce mainly IgM antibodies with low affinity and broad specificity. They do not undergo SHM or CSR and have limited memory potential.

B cells express various surface molecules that play important roles in their development, activation, and interaction with other cells. These include:

• MHC class II molecules, which present antigenic peptides to T cells and receive co-stimulatory signals from CD40L on T cells.
• Co-stimulatory molecules, such as CD80, CD86, CD40, and ICOSL, which enhance the activation and survival of B cells and T cells.
• Cytokine receptors, such as IL-4R, IL-6R, IL-10R, and BAFF-R, which modulate the proliferation, differentiation, and isotype switch of B cells.
• Homing molecules, such as L-selectin, CCR7, CXCR5, and integrins, which direct the migration and localization of B cells in different tissues.

B-cell differentiation in mammals is a complex and dynamic process that generates a diverse and adaptive immune system capable of recognizing and eliminating a wide range of pathogens. It is also regulated by multiple mechanisms to prevent autoimmunity and maintain immune tolerance.

B-cell development is a complex process that involves multiple stages of differentiation and selection. The goal of B-cell development is to generate a diverse repertoire of B cells that can recognize and respond to a variety of antigens, while avoiding self-reactivity and autoimmunity. B-cell development occurs mainly in the bone marrow, where hematopoietic stem cells (HSCs) give rise to common lymphoid progenitors (CLPs) that are committed to the lymphoid lineage. CLPs then differentiate into pro-B cells, which initiate the rearrangement of the immunoglobulin (Ig) heavy chain genes through a process called V(D)J recombination. This involves the random joining of variable (V), diversity (D), and joining (J) gene segments to form a functional heavy chain gene. Pro-B cells then express a pre-B cell receptor (pre-BCR) on their surface, which consists of the rearranged heavy chain paired with a surrogate light chain and the signal transduction molecules Igα and Igβ. The pre-BCR signals the pro-B cells to proliferate and progress to the pre-B cell stage, where they undergo rearrangement of the Ig light chain genes. This results in the expression of a complete B cell receptor (BCR) on the surface of immature B cells, which is composed of the heavy and light chains and Igα and Igβ. The BCR is specific for a certain antigen and determines the fate of the immature B cell.

Immature B cells undergo a process of negative selection in the bone marrow, where they are tested for self-reactivity. If the BCR binds to a self-antigen with high affinity, the immature B cell is either deleted by apoptosis or undergoes receptor editing, which is another round of light chain rearrangement that may generate a non-self-reactive BCR. If the BCR does not bind to any self-antigen or binds with low affinity, the immature B cell is allowed to exit the bone marrow and migrate to the spleen, where it matures further. In the spleen, immature B cells pass through transitional stages (T1 and T2) before differentiating into mature B cells that express both IgM and IgD on their surface. Mature B cells can be classified into two main subsets: follicular (FO) B cells and marginal zone (MZ) B cells. FO B cells circulate between the blood and the lymphoid follicles, where they encounter antigens and interact with T cells. MZ B cells reside in the marginal zone of the spleen, where they respond to blood-borne antigens and provide rapid antibody responses.

In addition to FO and MZ B cells, there is another subset of mature B cells called B-1 cells, which are derived from a distinct lineage of CLPs in the fetal liver . B-1 cells are located mainly in the peritoneal and pleural cavities, where they produce natural antibodies against common pathogens and self-antigens. B-1 cells have limited diversity and undergo little or no somatic hypermutation or class switch recombination.

B-cell development is regulated by various transcription factors, cytokines, chemokines, and cell-cell interactions that influence the survival, proliferation, differentiation, and selection of B cells at each stage . The outcome of B-cell development is a pool of diverse and functional B cells that can mount humoral immune responses against foreign antigens while maintaining self-tolerance.

One of the challenges of the immune system is to generate a diverse repertoire of B cells that can recognize a wide range of foreign antigens, while avoiding the production of B cells that react with self-antigens and cause autoimmune diseases. To achieve this balance, the immune system employs several mechanisms of tolerance that eliminate or inactivate self-reactive B cells at different stages of their development and activation.

The first checkpoint of B-cell tolerance occurs in the bone marrow, where immature B cells express IgM on their surface as part of the B-cell receptor (BCR). The BCR is responsible for binding and recognizing antigens, and initiating signaling pathways that regulate B-cell survival, proliferation and differentiation. If the BCR binds to a self-antigen that is present in the bone marrow environment, such as a cellular component or a serum protein, the immature B cell receives a negative signal that triggers apoptosis (programmed cell death) or anergy (functional unresponsiveness). This process is called negative selection or clonal deletion, and it eliminates about 50-75% of immature B cells in humans.

However, not all self-antigens are expressed or accessible in the bone marrow, and some immature B cells may escape negative selection and migrate to the periphery with self-reactive BCRs. To prevent these cells from causing autoimmunity, the immune system has a second checkpoint of B-cell tolerance in the spleen, where immature B cells undergo further maturation and differentiation into mature B cells that express both IgM and IgD on their surface. In the spleen, immature B cells encounter blood-borne antigens and receive survival signals from other cells and molecules. If the BCR binds to a self-antigen that is present in the blood or on the surface of other cells, such as red blood cells or platelets, the immature B cell receives another negative signal that induces apoptosis or anergy. This process is called receptor editing or receptor revision, and it eliminates about 5-10% of immature B cells in humans.

Receptor editing involves the reactivation of V(D)J recombination in the light-chain genes of the self-reactive BCR, resulting in the replacement of the original light chain with a new one that may have a different antigenic specificity. If the new light chain generates a BCR that is no longer self-reactive, the immature B cell is rescued and allowed to mature. If the new light chain generates a BCR that is still self-reactive, the immature B cell undergoes further receptor editing or apoptosis. Receptor editing can occur multiple times in an immature B cell until a non-self-reactive BCR is generated or the cell dies.

By deleting or editing self-reactive immature B cells in the bone marrow and spleen, the immune system ensures that most mature B cells have a low affinity for self-antigens and a high affinity for foreign antigens. However, some self-reactive mature B cells may still escape these checkpoints and enter the circulation or lymphoid tissues. These cells are subject to additional mechanisms of peripheral tolerance that prevent them from being activated by self-antigens or limit their effector functions. These mechanisms include ignorance, anergy, suppression by regulatory T cells (Tregs), and activation-induced cell death (AICD).

: Abbas AK, Lichtman AH, Pillai S. Cellular and Molecular Immunology. 9th ed. Elsevier; 2017.

Mature B cells are the final product of the B cell development stages that take place in the bone marrow. They express both IgM and IgD on their cell surface, with identical antigen specificity. They also express various CD molecules, such as CD19, CD20, CD21 and CD40, that help them interact with other cells and molecules of the immune system. Mature B cells are ready to respond to foreign antigens, but they need to undergo further differentiation and activation in the secondary lymphoid organs, such as the spleen and lymph nodes.

In the secondary lymphoid organs, mature B cells encounter antigens that are transported by specialized cells called antigen-presenting cells (APCs). Depending on the nature of the antigen and the presence or absence of T cell help, mature B cells can follow different pathways of activation and differentiation.

One pathway is the T cell-dependent pathway, which involves antigens that require T cell help to induce B cell antibody synthesis. These antigens are called thymus-dependent antigens (TDAs). TDAs are usually proteins that have multiple epitopes that can be recognized by both B cells and T cells. The interaction of T-helper cells and B cells takes place predominantly in the germinal centers of secondary lymphoid organs. Events in the germinal center reaction include somatic hypermutation of genes coding for antibody V regions, resulting in affinity maturation, and class switch recombination, in which a B cell that was synthesizing IgM and IgD switches to synthesizing antibody of a different isotype (IgG, IgA, or IgE) with the same antigenic specificity. Cytokines synthesized by T cells influence the isotype of antibody synthesized by the B cell. Germinal center B cells develop into memory B cells or plasma cells. Memory cells “home” to different tissues; plasma cells home predominantly to bone marrow where they continue to synthesize antibody for a long time.

Another pathway is the T cell-independent pathway, which involves antigens that do not require T cell help to induce B cell antibody synthesis. These antigens are called thymus-independent antigens (TIAs). TIAs are usually polysaccharides or lipids that have repetitive structures that can cross-link multiple B cell receptors on the same B cell. The cross-linking provides a strong signal for B cell activation and proliferation. However, TIAs do not induce somatic hypermutation or class switch recombination, so the antibodies produced by this pathway are mostly IgM with low affinity. B-cell responses to TIAs involve other sets of B cells—marginal-zone B cells and B-1 cells—and generate almost exclusively IgM.

In summary, mature B cells undergo further development in the secondary lymphoid organs, where they encounter antigens and differentiate into antibody-secreting plasma cells or memory B cells. The type of antigen and the availability of T cell help determine the pathway of activation and differentiation that B cells follow.

Thymus-dependent antigens (TD-Ags) are complex molecules that have multiple epitopes, or regions that can be recognized by different receptors on immune cells. TD-Ags require the cooperation of helper T cells (Th cells) to activate B cells and induce antibody production. TD-Ags include proteins, polypeptides, hapten-carrier complexes, and many pathogens such as viruses and bacteria.

The interaction of Th cells and B cells takes place mainly in the germinal centers of secondary lymphoid organs, such as lymph nodes and spleen. Germinal centers are specialized sites where B cells undergo proliferation, somatic hypermutation, class switch recombination, and differentiation into memory B cells or plasma cells .

The process of B cell activation by TD-Ags involves the following steps :

• B cells capture and process TD-Ags by endocytosis and present them on their surface in association with MHC class II molecules.
• Th cells recognize the antigen-MHC complex on B cells with their T cell receptors (TCRs) and co-receptors (CD4 molecules).
• Th cells also bind to other molecules on B cells, such as CD40 and CD80, which provide co-stimulatory signals for B cell activation.
• Th cells secrete cytokines, such as interleukin-4 (IL-4) and interleukin-21 (IL-21), that promote B cell proliferation and differentiation.
• Some B cells migrate to the germinal center, where they undergo somatic hypermutation of their immunoglobulin genes, resulting in increased affinity for the antigen.
• Some B cells also undergo class switch recombination, which changes the constant region of their immunoglobulin genes, resulting in different antibody isotypes (IgG, IgA, or IgE) with the same antigen specificity.
• Th cells provide further help to B cells in the germinal center by expressing CD40 ligand (CD40L) and inducible co-stimulator ligand (ICOSL), which enhance B cell survival and selection.
• Some B cells differentiate into memory B cells, which can respond more rapidly and effectively to the same antigen in the future.
• Some B cells differentiate into plasma cells, which secrete large amounts of antibodies into the blood and mucosal fluids.

The humoral immune response to TD-Ags is characterized by isotype switching, affinity maturation, and memory formation. These features allow the immune system to adapt to different types of antigens and provide long-lasting protection against infections .

One of the main outcomes of the interaction between T-helper cells and B cells is the formation of germinal centers (GCs) in the secondary lymphoid organs. GCs are specialized microenvironments where antigen-activated B cells undergo two important processes: somatic hypermutation (SHM) and class switch recombination (CSR).

SHM introduces random point mutations in the immunoglobulin (Ig) variable region genes, resulting in a diverse pool of B cells with different affinities for the antigen. CSR, on the other hand, replaces the Ig constant region gene for a different one, changing the antibody isotype (or class) without altering its antigen specificity. CSR allows B cells to produce antibodies with different effector functions, such as IgG, IgA, or IgE.

CSR is initiated by the transcription of germline transcripts (GLTs), which are non-coding RNAs that contain the switch regions of the Ig heavy chain locus. The switch regions are repetitive DNA sequences that serve as targets for the enzyme activation-induced cytidine deaminase (AID), which catalyzes the deamination of cytosine to uracil. This leads to DNA breaks and recombination between different switch regions, resulting in the deletion of the intervening DNA and the joining of a new constant region gene to the rearranged variable region gene.

The expression of GLTs and AID is regulated by several factors, including cytokines produced by T cells, transcription factors, and epigenetic modifications. For example, interleukin-4 (IL-4) induces CSR to IgG1 and IgE, while transforming growth factor-β (TGF-β) induces CSR to IgA and IgG2b. BCL-6, a transcriptional repressor expressed by GC B cells, inhibits GLT expression and CSR, while AID expression is enhanced by factors such as NF-κB and STAT6.

Although CSR was traditionally considered to occur predominantly in GC B cells, recent studies have challenged this view and suggested that CSR is largely triggered before GC formation and is greatly diminished in GCs. This is supported by several lines of evidence, such as the early detection of GLTs upon T cell priming, the lack of GLT expression in most GC light zone B cells, and the phylogenetic analysis of switched and unswitched B cell clones. Moreover, CSR is repressed in GC B cells by multiple mechanisms, such as downregulation of APE1, an enzyme that removes uracil from DNA and facilitates AID-mediated DNA breaks.

Therefore, CSR is a dynamic process that occurs mainly before GC differentiation and is influenced by various signals from T cells and the microenvironment. CSR enables B cells to produce antibodies with different effector functions that can better protect against different types of pathogens.

Memory B cells and plasma cells are the two main outcomes of B cell activation by antigen. They account for the long-term humoral immunity elicited by infections and many vaccines. Memory B cells enter a resting state and persist over long periods of time in the lymphoid organs in the apparent absence of immunizing antigen. Plasma cells, on the other hand, migrate to the bone marrow or other tissues where they continue to synthesize and secrete antibody for a long time.

Memory B cells and plasma cells develop from germinal center B cells that have undergone somatic hypermutation and class switch recombination. These processes increase the affinity and diversity of the antibody repertoire. However, not all germinal center B cells become memory or plasma cells. Some undergo apoptosis or return to the naïve B cell pool.

The factors that determine the fate of germinal center B cells are not fully understood, but they involve both intrinsic and extrinsic signals. Some of the intrinsic factors include transcription factors (such as Bcl-6, Blimp-1, Pax-5, IRF4), epigenetic modifications, and microRNAs. Some of the extrinsic factors include cytokines (such as IL-4, IL-10, IL-21), chemokines (such as CXCL12, CXCL13), and interactions with T cells and follicular dendritic cells.

Memory B cells and plasma cells have different phenotypes and functions. Memory B cells express high levels of surface Ig (mostly IgG, IgA, or IgE) and other molecules that allow them to recognize antigen and mount a rapid and robust secondary immune response. Plasma cells lose their surface Ig and other B cell markers and become specialized in producing large amounts of antibody (mostly IgG, IgA, or IgE) that can neutralize pathogens or facilitate their clearance by other immune cells.

Memory B cells and plasma cells are also heterogeneous populations that can be further classified into subsets based on their location, phenotype, function, and longevity. For example, memory B cells can be divided into germinal center-dependent and germinal center-independent subsets, depending on their origin. Plasma cells can be divided into short-lived and long-lived subsets, depending on their survival.

The development of memory B cells and plasma cells is essential for maintaining humoral immunity and protecting against reinfection. However, dysregulation of these processes can also lead to autoimmune diseases or malignancies. Therefore, understanding the molecular mechanisms and cellular interactions that govern the generation and maintenance of these cell types is important for developing effective vaccines and therapies for various diseases.

Thymus-independent antigens (TI antigens) are antigens that can stimulate B cells to produce antibodies without the help of T cells. These antigens are usually less complex than thymus-dependent antigens (TD antigens) and often consist of polysaccharides or lipopolysaccharides (LPS) that have repeating epitopes . TI antigens mainly induce IgM synthesis by B cells and do not generate immunological memory.

TI antigens can be classified into two types: TI-1 and TI-2 antigens . TI-1 antigens are typically derived from bacterial cell walls, such as LPS, and have a direct mitogenic effect on B cells, meaning that they can activate B cells regardless of their antigen specificity and induce polyclonal antibody production . TI-1 antigens can also act as adjuvants for TD antigens by enhancing the signals through the B-cell receptor. TI-2 antigens are usually polysaccharides, glycolipids, or nucleic acids that have a high density of identical epitopes and can cross-link multiple B-cell receptors on the same B cell . TI-2 antigens require accessory cells, such as macrophages or dendritic cells, to provide interleukin-1 (IL-1) and other co-stimulatory signals for B-cell activation.

The main subsets of B cells that respond to TI antigens are marginal-zone B cells and B-1 cells. Marginal-zone B cells are located in the marginal zone of the spleen and are specialized in recognizing blood-borne TI-2 antigens, such as capsular polysaccharides of encapsulated bacteria. B-1 cells are found mainly in the peritoneal and pleural cavities and produce natural antibodies against common TI-1 antigens, such as LPS and phosphatidylcholine. Both marginal-zone B cells and B-1 cells have a limited repertoire of B-cell receptors and can undergo self-renewal in the periphery.

B-cell responses to TI antigens play an important role in the defense against extracellular bacteria, especially those that have polysaccharide capsules or LPS on their surface. However, these responses are also associated with some autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, in which self-reactive antibodies are produced against nuclear antigens or IgG. Therefore, the regulation of TI antigen responses is crucial for maintaining immune homeostasis.

B cells are the only cells that express membrane-bound immunoglobulins (Ig), which serve as their antigen receptors. The membrane Ig consists of a transmembrane antibody molecule (IgM, IgD, IgA, IgG, or IgE) and a signal transduction moiety composed of two proteins: Igα (CD79a) and Igβ (CD79b). The membrane Ig is also called the B cell receptor (BCR), as it initiates the activation and differentiation of B cells upon binding to a specific antigen.

In addition to membrane Ig, B cells express various surface molecules that are involved in different stages of B cell development and function. Some of these molecules are:

• CD10: A metalloproteinase that is expressed on early B cells in the bone marrow and on germinal center B cells in secondary lymphoid organs. It is involved in the cleavage of cell surface molecules and the regulation of B cell proliferation and differentiation.
• CD19: A co-receptor that forms a complex with CD21, CD81, and CD225 on mature B cells. It enhances the signaling through the BCR and lowers the threshold for antigen activation. It also participates in the regulation of B cell survival, tolerance, and memory.
• CD20: A transmembrane protein that is expressed on most mature B cells, but not on plasma cells. It is involved in the modulation of BCR signaling and calcium influx. It is also a target for monoclonal antibody therapy for some B cell malignancies.
• CD27: A member of the tumor necrosis factor receptor family that is expressed on memory B cells and plasma cells. It binds to its ligand CD70 on activated T cells and provides co-stimulatory signals for B cell activation, proliferation, and differentiation. It also plays a role in the generation and maintenance of long-lived plasma cells and memory B cells.

B cells also express major histocompatibility complex (MHC) class II molecules, which present processed antigens to helper T cells and receive co-stimulatory signals from them. Moreover, B cells express various co-stimulatory molecules, such as B7, CD40, and ICOSL, that interact with their counterparts on T cells and enhance the activation and differentiation of both cell types. Furthermore, B cells express receptors for cytokines, such as IL-4, IL-6, IL-10, and BAFF, that modulate their survival, proliferation, class switch recombination, and antibody secretion.

B cells also express homing molecules that allow them to migrate to specific tissues and sites of inflammation. For example, B cells express integrins, such as LFA-1 and VLA-4, that mediate their adhesion to endothelial cells and extracellular matrix. They also express chemokine receptors, such as CXCR4 and CXCR5, that direct their migration to lymphoid organs and germinal centers.

In summary, B cells express a variety of surface molecules that enable them to recognize antigens, receive signals from other cells, modulate their responses, and migrate to appropriate locations.

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