ABSTRACT
General 238 The B lymphocyte/plasma cell lineage 238 Activation of B lymphocytes to become plasma cells 239 In vitro differentiation of B cells to become plasma cells 239 Major in vivo sites of plasma cell formation 240 Rapid humoral responses 240 Germinal center-related immune responses 241 Gastrointestinal lamina propria plasma cells 242 Plasma cell accumulations 243
Lymphoid neogenesis and chronic inflammation 243 Castleman disease, IL-6 transgenic mice 243 Gastrointestinal plasma cell accumulations 244 Reactive plasmacytosis 244 Proliferation disorders of plasma cells 245 Monoclonal gammopathy of undetermined significance 245 Multiple myeloma 246 Key points 246 References 246
The B lymphocyte/plasma cell lineage has three general developmental stages. In mammals the first takes place in the bone marrow. Here, closely linked but separate immunglobulin (Ig) structural genes that code for heavy (H) and light (L) chains are assembled and joined on the chromosome to form a template for transcription. For the H chain, four genes are rearranged from their germline configuration and brought together in two steps: first, one of 17-19 DH genes is joined to one of the 5 JH genes that are linked to Cμ; second, one of 100 functional VH genes is joined to the 5-selected DH gene now joined to JH and Cμ. For the L chain, where there is no D element, rearranged Ig DNA is formed by the joining of one of 50-100 VL genes to one of 5 JL genes. The newly synthesized H and L chains are folded, assembled, glycosylated, and then joined together to form the antigen-binding receptor, also called the B cell receptor (BCR). The complex steps in this process are described in Chapter 9. The second developmental stage takes place after the B lymphocyte, with its individual or idiotypic BCR, is released into the peripheral B cell pool where it circulates in and out of lymphoid tissues and inflammatory sites in search of a complementary antigenic structure. Appropriate binding to antigen by a T cell:B cell
macromolecules cause the B cell to proliferate and undergo clonal expansion. This process is described in Chapter 11. In the third and final developmental stage, the BCR-positive cell transforms into a professional Ig-secreting plasma cell, the subject of the present chapter. Very simplistically, the substeps in this process are the activated B lymphocyte becomes a plasmablast (with proliferative potential), then the plasmablast matures to intermediate plasma cell and finally to post-mitotic plasma cell. Some of the latter go on to become over-ripe: Mott cells. The anatomical sites where plasma cells develop are listed in Table 14.1.
