Plasma cell differentiation and multiple myeloma.

Microarray analyses and gene targeting have recently enhanced the understanding of factors involved in normal plasma cells and multiple myeloma. Plasma cells develop from marginal zone or germinal center B cells following stimulation by antigen, microbial products, TNF family signals and cytokines. Transcription factors, B-lymphocyte-induced maturation protein 1 (Blimp-1) and X-box binding protein 1 (XBP-1) are required for plasma cell development. They regulate sets of genes that induce immunoglobulin secretion, halt proliferation and block alternative B-cell fates. In multiple myeloma, transforming events lead to proliferation and survival, but programs for plasma cell differentiation and the inhibition of B-cell genes appear to be largely intact.