Abstract
Immunoglobin heavy (H) chains are composed of a variable (VH) and a constant (CH) region. The latter is encoded respectively by eight distinct genes for the classes and subclasses in mice—Cμ, Cδ, Cγ3, Cγ1, Cγ2b, Cγ2a, Cɛ and Cα genes—arrayed in that order on the chromosome1. During differentiation of a single B lymphocyte, a given VH region is first expressed as a μ chain, followed by the switch of the CH region to other classes such as δ, γ, ɛ and α. The molecular genetic basis for this phenomenon, called heavy chain class switch, has been elucidated recently by cloning and characterization of immunoglobulin genes of mouse myelomas secreting various classes of immunoglobulin2–4. By this model, DNA rearrangement, called S–S recombination, brings a VH gene, located originally 5′ to the Cμ gene, close to another CH gene by deletion of an intervening DNA segment5–9. The S–S recombination occurs between S regions located in the 5′ flanking region of each CH gene. The nucleotide sequences of S regions comprise tandem repetitive sequences sharing short common sequences10–14. In contrast, the expression of surface IgD in μ+ δ+ lymphomas and in normal μ+ δ+ lymphocytes seems not to involve DNA rearrangement in the region between the Cμ and Cδ genes15,16. The simultaneous expression of the Cμ and Cδ genes with a single VH gene may be mediated by two alternative routes of RNA processing of a primary nuclear transcript containing the VH, Cμ and Cδ genes. We have now studied the organization of CH genes in sorted μ+ɛ+ B lymphocytes and found that they retain Cμ, Cδ, Cγ and Cɛ genes, suggesting that the simultaneous expression of the Cμ and Cɛ genes is mediated by an RNA splicing mechanism. We propose that class switching requires at least two steps of differentiation, the first step involving activation of differential splicing and the second the DNA rearrangement.
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Yaoita, Y., Kumagai, Y., Okumura, K. et al. Expression of lymphocyte surface IgE does not require switch recombination. Nature 297, 697–699 (1982). https://doi.org/10.1038/297697a0
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DOI: https://doi.org/10.1038/297697a0
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