B Lymphocytes


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 .



Allman D, Lindsley RC, De Muth W et al. (2001) Resolution of three nonproliferative immature splenic B cell subsets reveals multiple selection points during peripheral B cell maturation. Journal of Immunology 167(12): 6834–6840.

Bondada S and Garg M (1994) Thymus independent antigens. In: Snow EC (ed.) Handbook of B and T Lymphocytes, pp. 343–370. New York: Academic Press.

Bondada S, Wu HJ, Robertson DA and Chelvarajan RL (2001) Accessory cell defect in unresponsiveness of neonates and aged to polysaccharide vaccines. Vaccine 19: 557–565.

Calame KL (2001) Plasma cells: finding new light at the end of B cell development. Nature Immunology 2(12): 1103–1108.

Chung JB, Silverman M and Monroe JG (2003) Transitional B cells: step by step towards immune competence. Trends in Immunology 24(6): 343–349.

Coca A and Sanz I (2012) Updates on B‐cell immunotherapies for systemic lupus erythematosus and Sjogren's syndrome. Current Opinion in Rheumatology 24(5): 451–456.

Cyster JG and Goodnow CC (1997) Tuning antigen receptor signaling by CD22: integrating cues from antigens and the microenvironment. Immunity 6(5): 509–517.

Desiderio S (1997) Role of btk in B cell development and signaling. Current Opinion in Immunology 9: 534–540.

Foy TM, Aruffo A, Bajroth J, Buhlman JE and Noelle RJ (1996) Immune regulation by CD40 and its ligand gp39. Annual Review of Immunology 14: 591–617.

Ghosn EE, Yamamoto R, Hamanaka S et al. (2012) Distinct B‐cell lineage commitment distinguishes adult bone marrow hematopoietic stem cells. Proceedings of the National Academy of Sciences of the USA 109(14): 5394–5398.

Gold MR and De Franco AL (1994) Biochemistry of B lymphocyte activation. Advances in Immunology 55: 221–295.

Greenwald RJ, Latchman YE and Sharpe AH (2002) Negative co‐receptors on lymphocytes. Current Opinion in Immunology 14(3): 391–396.

Gururajan M, Jacob J and Pulendran B (2007) Toll‐like receptor expression and responsiveness of distinct murine splenic and mucosal B‐cell subsets. PLoS One 2: e863.

Janeway CA and Travers P (1997) Immunobiology. New York: Garland Publishing Inc and London: Current Biology Ltd.

Kantor AB and Herzenberg LA (1993) Origin of murine B cell lineages. Annual Review of Immunology 11: 501–538.

Ke J, Gururajan M, Kumar A et al. (2006) The role of MAPKs in B cell receptor‐induced down‐regulation of Egr‐1 in immature B lymphoma cells. Journal of Biological Chemistry 281(52): 39806–39818.

Martin F and Kearney JF (2002) Marginal zone B cells. Nature Reviews Immunology 2(5): 323–335.

Melchers F and Rolink A (1999) B‐lymphocyte development and biology, In: Paul NE (ed.) Fundamental Immunology, pp. 183–224. Philadelphia, PA: Lippincott‐Raven.

Montecino‐Rodriguez E and Dorshkind K (2012) B‐1 B cell development in the fetus and adult. Immunity 36(1): 13–21.

Murphy K (2011) Janeway's Immunobiology, 8th edn, Chap. 1, 4, 5 and 10. New York: Garland Science.

Murphy KM (2012) Janeway's Immunobiology. New York: Garland Science.

Niiro H and Clark EA (2002) Regulation of B‐cell fate by antigen‐receptor signals. Nature Reviews Immunology 2(12): 945–956.

Parker DC (1993) T dependent B cell activation. Annual Review of Immunology 11: 331–360.

Rajewsky K (1996) Clonal selection and learning in the antibody system. Nature 381: 751–758.

Sen G, Wu HJ, Bikah G et al. (2002) Defective CD19‐dependent signaling in B‐1a and B‐1b B lymphocyte subpopulations. Molecular Immunology 39(1–2): 57–68.

Sindhava V, Woodman ME, Stevenson B and Bondada S (2010) Interleukin‐10 mediated autoregulation of murine B‐1 B‐cells and its role in Borrelia hermsii infection. PLoS One 5(7): e11445.

Sindhava VJ and Bondada S (2012) Multiple regulatory mechanisms control B‐1 B cell activation. Frontiers in Immunology 3: 372. doi: 10.3389/fimmu.2012.00372.

Su TT and Rawlings DJ (2002) Transitional B lymphocyte subsets operate as distinct checkpoints in murine splenic B cell development. Journal of Immunology 168(5): 2101–2110.

Tuscano JM, Harris GS and Tedder TF (2003) B lymphocytes contribute to autoimmune disease pathogenesis: current trends and clinical implications. Autoimmune Reviews 2(2): 101–108.

Victora GD and Nussenzweig MC (2012) Germinal Centers. Annual Review of Immunology 30: 429–457.

Yoshizaki A, Miyagaki T, DiLillo DJ et al. (2012) Regulatory B cells control T‐cell autoimmunity through IL‐21‐dependent cognate interactions. Nature 491(7423): 264–268.

Further Reading

Gause WC and Lu P (1996) Cellular sources and regulation of cytokine production. In: Snapper CM (ed.) Cytokine Regulation of Humoral Immunity: Basic and Clinical Aspects, pp. 141–158. Chichester, UK: Wiley.

Ghia P, ten Boekel E, Rolink AG and Melchers F (1998) B‐cell development: a comparison between mouse and man. Immunology Today 19: 480–485.

Germain RN (1994) Antigen processing and presentation. In: Paul WE (ed.) Fundamental Immunology, pp. 629–676. New York: Raven Press.

Haughton G, Arnold LW, Whitmore AC and Clark SH (1993) B‐1 cells are made, not born. Immunology Today 14: 84–87.

Janeway CA Jr, Travers P, Walport M et al. (2001) Immunobiology: The Immune System in Health and Disease, 5th edn. New York: Garland Science.

Kishimoto T (1988) Molecular regulation of B lymphocyte response. Annual Review of Immunology 6: 485–512.

Liu YJ, Johnson GD, Gordon J and Maclennan IC (1992) Germinal centers in T‐cell‐dependent antibody responses. Immunology Today 13: 17–21.

Mackay F, Schneider P, Rennert P and Browning J (2003) BAFF and APRIL: a tutorial on B cell survival. Annual Review of Immunology 21: 231–264.

Mond JJ, Lees A and Snapper CM (1995) T cell‐independent antigens type 2. Annual Review of Immunology 13: 655–692.

Monroe JG (1996) Tolerance sensitivity of immature‐stage B cells: can developmentally regulated B cell antigen receptor (BCR) signal transduction play a role? Journal of Immunology 156: 2657–2660.

Snapper CM and Finkleman FD (1994) Immunoglobulin class switching. In: Paul WE (ed.) Fundamental Immunology, pp. 837–864. New York: Raven Press.

Tedder TF, Inaoki M and Sato S (1997) The CD19–CD21 complex regulates signal transduction threshold governing humoral immunity and autoimmunity. Immunity 6: 107–118.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
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]