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

摘要: We have used Southern9s blotting technique to determine the extent which genes encoding constant (C) regions of μ, α, γ1, and γ2b immunoglobulin heavy (H) chains are altered in number context from their germline (embryo) state a series 14 plasmacytomas expressing various H chain classes. In three μ chain-producing studied there was no evidence rearrangement CH other than Cμ. contrast, deletion nonexpressed frequent that produce γ or α chains. The observed pattern deletions is consistent with idea ontogenetic switch class requires gene deletion. Frequently, though not always, such as well types occur both allelic loci. Particularly noteworthy γ2a-expressing tumors Cα evident alleles. incorporate these observations into probabilistic model B cell development: first phase, may between Cμ variable (VH) array, result formation productive fused VH-Cμ gene. then enter second allows within arrays homologous chromosomes. Some juxtapose expressed VH switch; others delete alter without changing phenotype cell. predict switching can be single-step multi-step process, latter case those rearrangements do physiologically significant they limit options further switching.