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. 1980 Mar;77(3):1422–1426. doi: 10.1073/pnas.77.3.1422

Rearrangement of immunoglobulin heavy chain genes during B-lymphocyte development as revealed by studies of mouse plasmacytoma cells

C Coleclough 1, D Cooper 1, R P Perry 1
PMCID: PMC348507  PMID: 6769113

Abstract

We have used Southern's blotting technique to determine the extent to which the genes encoding the constant (C) regions of μ, α, γ1, and γ2b immunoglobulin heavy (H) chains are altered in number and context from their germline (embryo) state in a series of 14 plasmacytomas expressing various H chain classes. In the three μ chain-producing plasmacytomas studied there was no evidence of rearrangement of CH genes other than Cμ. In contrast, rearrangement and deletion of nonexpressed CH genes was frequent in plasmacytomas that produce γ or α chains. The observed pattern of deletions is consistent with the idea that the ontogenetic switch in H chain class requires CH gene deletion. Frequently, though not always, such deletions as well as other types of rearrangement occur in both allelic loci. Particularly noteworthy are three γ2a-expressing tumors in which Cα gene rearrangement is evident in both alleles. We incorporate these observations into a probabilistic model of B cell development: in the first phase, deletions may occur between the Cμ gene and the variable (VH) gene array, which result in the formation of a productive fused VH-Cμ gene. The cell may then enter a second phase, which allows deletions within the CH gene arrays of both homologous chromosomes. Some deletions juxtapose the expressed VH gene with a second CH gene and result in a H chain class switch; others delete or alter the context of CH genes without changing the phenotype of the cell. We predict that switching can be both a single-step and a multi-step process, and that in the latter case those rearrangements that do not result in a switch may be physiologically significant in that they may limit the options of further switching.

Keywords: heavy chain constant region genes, gene rearrangement, heavy chain class switch

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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