B Lymphocytes

Abstract

Bone marrow‐derived (B) lymphocytes are antibody‐producing cells in the body. Antibody production is initiated on recognition of antigen via a specific immunoglobulin receptor, and reception of growth and differentiation signals. B lymphocytes are also important for the activation of helper T lymphocytes and are integral for the memory component of the immune response. A variety of B cell subsets exist that have distinct phenotypes and functions. Effector B cells mediate B‐cell responses to antigens and vaccines, whereas regulatory B cells mediate suppression of T cells. In addition to antibody secretion, B cells present antigen to T cells, and B‐cell secretion of soluble factors like cytokines and chemokines is important for B‐cell responses to infectious diseases. Excessive or uncontrolled B‐cell activation lead to the development of B‐cell lymphoma and autoimmune diseases. Therapeutic antibodies that deplete B cells are in clinical use for the treatment of B‐cell lymphomas and B cell‐mediated autoimmune diseases.

Key Concepts:

  • B cells develop in the bone marrow.

  • B lymphocytes mediate antibody responses.

  • B cell maturation occurs in the bone marrow and in the spleen.

  • Mature B cells reside in the secondary lymphoid organs like spleen and lymph nodes.

  • B cell subsets are defined by surface marker expression and phenotypic characteristics.

  • Thymus independent (TI) antigens activate B cells without a need for antigen‐specific helper T cells. Thymus‐dependent (TD) antigens have an obligate requirement for cognate interaction with antigen‐specific helper T cells to activate B cells.

  • B cells differentiate into plasma cells that secrete antibodies.

  • Antibodies bind to antigens and neutralise the infection (neutralising antibodies).

  • B cell depletion is an effective therapy in B lymphoma and autoimmune diseases.

Keywords: antibodies; B‐1 cells; B‐2 cells; cytokines; isotype switching; memory cells; thymus‐independent antigens; thymus‐dependent antigens

Figure 1.

B‐lymphocyte activation. (a) Transmission electron micrographs of various stages of activation of lymphocytes. (1) Shows a small resting lymphocyte (T or B cell) with a large nucleus and little or no endoplasmic reticulum. (2) Shows an activated lymphocyte called a lymphoblast. (3) Shows activated effector B (plasma cell) (left) and T cells (right). Plasma cells have extensive rough endoplasmic reticulum, which is critical for the synthesis and secretion of large quantities of antibodies. Effector T cells also have a large cytoplasm devoted to the secretion of cytokines. Reproduced from Rooney N, University of Bath, Bath, UK with permission from Garland Publishing Inc. (b) Schematic representation of various stages of B‐lymphocyte activation. Resting B cells respond to antigen (Ag) and signals from other accessory cells by activation and maturation to plasma cells that secrete immunoglobulin(Ig) M. Some of the activated B cells switch to plasma cells that secrete other immunoglobulin isotypes, whereas others become memory cells that are quiescent.

Figure 2.

Development and differentiation of B cells. Pre‐pro‐B cells are the earliest precursors that arise from bone marrow stem cells and are committed to B lineage. Varying degrees of expression (change in line thickness) or lack of expression (no line) of surface markers at each developmental stage is indicated. The status of various immunoglobulin (Ig) genes is given at the bottom. HSA, heat‐stable antigen; CD, cluster of differentiation; MHC, major histocompatibility complex.

Figure 3.

Diagrammatic representation of an IgM antibody molecule. Antibody molecules are present on a B‐cell membrane with the antigen‐binding sites and majority of the molecules are exposed on the outside of the cell surface. This is anchored by a transmembrane domain with a three amino acid‐long cytoplasmic tail. The coreceptors, immunoglobulin (Ig) α and Igβ, have large cytoplasmic domains that allow interaction with the signal transduction machinery in the cell.

Figure 4.

In the bone marrow, B‐cell lineage starts from the committed multipotent stem cell. First, pro‐B cells are formed and they mature into pre‐B cells. During this differentiation process, B cells start rearranging their immunoglobulin heavy‐chain loci. Pre‐B cells differentiate into immature B cells, which express both heavy and light chains. During this process, both self‐reactive and nonself‐reactive B cells are generated. Self‐reactive immature B cells will make repeated attempts to generate nonself‐reactive BCR (receptor editing) or get clonally deleted. The immature B cells exit the bone marrow and enter the spleen as transitional 1 (T1) B cells. T1 cells mature into T2 cells. Finally, transitional cells differentiate into mature follicular B cells. Abbreviation: MZ, marginal zone; PALS, periarteriolar lymphoid sheath. Reprinted from Chung et al. with permission from Elsevier, © 2003.

Figure 5.

B‐cell activation by T‐independent and T‐dependent antigens. (a) T‐independent activation. Polysaccharide antigens with a large number of repeating epitopes allow efficient crosslinking of B‐cell receptors and initiate direct B‐cell activation. The activated B cell matures into a plasma cell in the presence of accessory signals. (b) T‐dependent activation. Proteins and other small molecules that have a limited number of epitopes require T‐cell help for activating B cells. The sequence of events is: (1) the proteins are taken up by B cells or other antigen‐presenting cells and are degraded into small peptides that associate with major histocompatibility complex (MHC) class II molecules; (2) the peptide–MHC complex is recognised by the T‐cell receptor (TCR), allowing T‐cell activation via TCR and CD28; (3) the activated T cells express CD40L, which in turn provides important growth signals to B cells in the context of other surface molecules, resulting in B‐cell activation. AFC, antibody forming cell; Ag, antigen; BCR, B‐cell receptor. Modified from Bondada and Garg .

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Bondada, Subbarao, Chelvarajan, Ralph L, and Gururajan, Murali(May 2013) B Lymphocytes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001121.pub3]