Immunoglobulin heavy-chain constant-region genes

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Antibodies are composed of two identical heavyand light-chain polypeptides. Each heavy and light chain contains an amino-terminal variable (V) region, responsible for antigen recognition, and a carboxy-proximal constant(C) region, which participates in a variety of immunological processes, including effector-cell recognition and complement fixation. The variable regions are encoded by several hundred germ-line genes, while a limited member of genes encode the constant regions. The mouse CH gene locus resides on the distal arm of chromosome 12 and consists of eight genes (p, 6, 73, yl , y2b, y2a, E and a) that span close to 200 kb of DNA (see figure) (Shimizu et al., Cell 28, 499-506, 1982). The mouse CH gene cluster contains no well conserved pseudo-& genes. &-coding regions are composed of either two (6) three (~3, yl , y2b, (II) or four (cl and E) structural domains, each consisting of -100 amino acids that are separated by small introns. Antibodies of immature B lymphocytes possess hydrophobic carboxy-terminal CH extensions, allowing these molecules to function as transmembrane proteins. Hydrophobic membrane domains are separated from the secreted termini of CH genes by a -2 kb intron (Early et al., Cell 20, 313-319, 1980). Membrane-bound or secreted antibody is thought to be expressed first by regulation of the site of transcriptional termination or poly(A) addition and then by sitespecific RNA splicing (Early et al., op. cit.; Rogers et al., Cell 26, 19-27, 1981). The human CH gene family consists of at least nine functional members (p, 6, yl , 72, y3,y4, c, al and a2). As in the mouse, the human CS gene is located several kilobases 3’ of C,” (Rabbitts et al., NAR 9,4509-4524, 1981). The four human gamma genes display more extensive homology to each other than is observed among the mouse gamma genes, and at least two Minireviews