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Abstract

B lymphocytes may switch from producing an immunoglobulin heavy chain of the μ class to that of the γ, ε or α class1–4. To maintain the specificity, the new heavy chain must keep the original variable (V) region; this is achieved by deleting DNA sequences so that the V (consisting of joined VH, diversity (DH) and joining (JH) gene segments) and C (constant) gene segments coding for the new heavy chain are brought into close proximity (reviewed in ref. 5; we do not consider here the μ–δ situation). There are, in principle, three types of chromosomal rearrangements that yield a deletion: (1) rearrangement within a chromatid; (2) unequal sister chromatid exchange (as suggested by Obata et al.6); and (3) unequal recombination between chromosomal homologues. We have analysed the arrangement of Cμ DNA in clones of the pre-B-cell line 18–81 that switches in vitro from μ to γ2b (ref.7). The clones examined produce either μ, γ2b or no immunoglobulin chain. We report here that all the γ2b clones had lost at least one copy of Cμ and no clones contained three copies of Cμ. These findings formally exclude both unequal sister chromatid exchange and recombination between homologues as mechanisms for creating a gene encoding the γ2b chain.