chapter  Chapter 5
38 Pages

B Cells and Humoral Immunity

WithConstantin A. Bona, Francisco A. Bonilla

As we gain more and more information regarding the early genetic events in the commitment of lymphocyte precursors to the B cell pathway, it becomes possible to make finer distinctions of phenotype, each with a particular genetic correlate (i.e., the expression of particular genes and their products). Because of this, there are several current systems for naming early stages of B cell development. We shall divide B lymphocyte differentiation into the following stages: stem cell; progenitor cell or null cell; pre-B cell; immature B cell; virgin B cell or mature B cell; B lymphoblast; plasma cell; and memory cell. All of the events leading up to the mature, or resting B cell stage take place in the liver during gestation, and in the bone marrow thereafter, and do not require interaction of B cells with the antigen which their immunoglobulin receptors ultimately will recognize. Thus, these stages are often called the antigen-independent phase of B cell development. Subsequent steps occur after B cells interact with antigen and regulatory T cells and are called the antigen-dependent phase. A general scheme of B cell differentiation is shown in Figure 5–1. Details of this scheme are elaborated below. <italic>B cell development</italic>. The generation of mature B cells from bone marrow stem cells is independent of antigen stimulation. Various stages of development are marked by rearrangement and expression of immunoglobulin genes, and the presence of particular surface markers. Further development of mature B cells depends on antigen stimulation. B cell development has been divided into 9 stages listed in order from left to right. Note that the nomenclature of the various stages may vary somewhat among authors. Note also that blasts may become either memory cells or plasma cells, and that memory cells may revert to blasts, proliferate, and then become plasma cells. Progression of precursors along this developmental pathway is subject to disruption at several stages (indicated by dashed arrows leading to cells marked with “X”=dead). Failure of expressible rearrangements of VDJ<sub>H</sub>, or VJ<sub>L</sub>, failure of a mature B cell to be stimulated by appropriate antigen/cellular contacts, or somatic mutations destroying antigen specificity may all derail B cell development. A partial list of B cell surface markers is shown at the left. Explanation of symbols and abbreviations: GL, germline; CS, classswitching; SM, somatic mutation; C, cytoplasmic expression; S, surface expression, parentheses indicate “where class-switching has not occurred;” +, marker is present on the cell surface, parentheses indicate “speculative;” CDX, cluster of differentiation antigen X (see <xref ref-type="book-part" rid="chapter2">Chapter 2</xref>); IL-XR, receptor for interleukin X. (Surface marker data adapted from <xref ref-type="bibr" rid="ref5_30">Uckun, 1990</xref>.)