Figure 1. B-lymphocyte activation: (a) transmission electron micrographs of various stages of activation of lymphocytes. The upper panel shows a small resting lymphocyte (T or B cell) with a large nucleus and little or no endoplasmic reticulum. The middle panel shows an activated lymphocyte called a lymphoblast. Lower panels show 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 secretion of cytokines. Courtesy of N. Rooney, University of Bath, Bath, UK (reproduced 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 molecule exposed on the outside of the cell surface. This is anchored by a transmembrane domain with a cytoplasmic tail three amino acids long. The coreceptors, immunoglobulin (Ig) and Ig, have large cytoplasmic domains that allow interaction with 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 chain. 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 cell. Abbreviation: MZ, marginal zone, PALS, periarteriolar lymphoid sheath. Reprinted from Chung et al. (2003) Copyright (2003), with permission from Elsevier.

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 recognized by 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 (1994).