immunoglobulin genes

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Genes encoding the light and heavy chains of the immunoglobulins. These genes are remarkable in that they are made up of segments that are shuffled as the B lymphocytes mature. The light chains contain segments that can be symbolized L-V, J, and C. The V, or variable, segment codes for the first 95 amino acids of the chain, whereas the C, or constant, segment codes for amino acids 108 to 214. The joining segment, J, codes for amino acids 96 to 107. L codes for a leader sequence 17–20 amino acids long; it functions in the transport of the molecule through the plasmalemma and is cleaved off the molecule in the process. There are about 300 L-V segments per light chain gene, and each of the V segments has a different base sequence. In the kappa gene, there are six J segments, each with a different base sequence, and one C segment. During differentiation of a given B lymphocyte stem cell, an immunoglobulin gene is assembled containing one L-V, one J, and one C segment, and this gene is transcribed by the lymphocyte and all of its progeny. The lambda gene also contains about 300 L-V segments, but each of the six J segments has its own adjacent C segment. The heavy chain gene is over 100,000 nucleotides long and contains a series of segments that can be symbolized L-V, D, J, Cμ, Cδ, Cγ3,Cγ1,Cγ2b, Cγ2a, Cε, and Cα. There are about 300 L-V segments, 10–50 D segments, 4 J segments, and one each of the C segments. Each D segment codes for about 10 amino acids. During differentiation the segments are shuffled so that the variable region of a heavy chain is encoded by a segment that contains one L-V, one D, and one J segment. The gene also contains mu, delta, gamma, epsilon, and alpha subsegments, and which one of these is transcribed determines the class to which the antibody will belong. See Chronology, 1965, Dreyer and Bennett; 1976, Hozumi and Tonegawa; 1981, Sakano et al..; 1987, Tonegawa; allelic exclusion, genomic equivalence, heavy chain class switching, immunoglobulin chains, transfectoma, V(D)J recombination.

Subjects: Genetics and Genomics.

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