Mechanisms that regulate immunoglobulin gene expression.

Abstract

The expression of genes encoding the lightand heavy-chain immunoglob­ ulin polypeptides is stringently regulated: (a) the genes are expressed only in cells of the B-lymphocyte lineage; (b) heavy-chain genes are expressed earlier in B-cell development than light-chain genes ; (c) after light-chain genes are activated, expression of the two chains is coordinately regulated; (d) levels of immunoglobulin gene products increase by several orders of magnitude as pre-B cells mature to terminally differentiated plasma cells; and (e) immunoglobulin molecules may be either displayed on the cell surface of B cells or secreted or both (1). Furthermore, the growth and maturation of B lymphocytes, with its concomitant changes in im­ munoglobulin gene expression, are modulated by a variety of signals received at the B-cell surface from antigen, T cells, or T-cell factors (2). Since their organization and structure are well-established (3), immunoglobulin genes provide an excellent opportunity to unravel a complex regulatory circuit and to understand the molecular bases for the exquisite sensitivity and control of the vertebrate immune system. Immunoglobulin genes also display several characteristics that appear to be unusual for eukaryotic genes; (a) DNA rearrangement is required for their expression (3); (b) only one of the two chromosomes is functionally expressed, a phenomenon called allelic exclusion (4); and (c) they appear to be members not only of three multigene families (5) but also of a supergene family which includes genes of the major histocompatibility complex, the T-cell receptor genes, and genes for other proteins found on the cell surface