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Translation

Heavy chain polypeptide

Figure 4 Diversity generated by VDJ recombination. The organization of a portion of the human immunoglobulin heavy chain locus containing the V, D and J gene segments is shown. The numbers refer to total number of gene segments including pseudo-genes. The union of one D gene segment to one JH gene segment occurs prior to one V gene segment joining to the -DJH pair. The leader intron is removed during RNA splicing. Alternative splicing can lead to either membrane bound (m) immunoglobulin, or secreted immunoglobulin (s) The approxi mate numbers of the gene segments are indicated. Ep, enhancer; Sp., p. switch region; pm, membrane-bound IgM; p.,, secreted IgM. The primary repertoire consists of V(D)J recombinations in the absence of antigen, producing predominantly antibodies which are polyspecific but of low affinity. The secondary repertoire consists of antibodies selected from the primary repertoire by antigen. These antibodies are characterized by mutation and high affinity for specific antigens. (Reproduced with permission from Okada A and Alt FW (1995) The variable region gene assembly mechanism. In: Honjo T and Alt FW (eds) Immunoglobulin Genes. London: Academic Press.)

families based on greater than 80% homology at the nucleotide level (Table 2). In the human, the VH family gene segments are interspersed as opposed to the mouse, where the VH gene segments from particular families are clustered. There are four DH clusters (D1-D4) each containing seven DH segments. Two orphon VH loci are located on chromosomes 15 and 16, some of which are potentially functional, although they are not associated with JH or C region genes. At least four orphon Dn clusters, each con-

Table 2 Human VH gene segments

Chromosome Vu familv

Table 2 Human VH gene segments

Chromosome Vu familv

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