Organization of immunoglobulin heavy chain genes and allelic deletion model.

Abstract

The number of times the gene sequence encoding constant regions of mouse immunoglobulin [Ig] heavy chains .gamma.1, .gamma.2a, and .gamma.3 are represented in the mouse genome was assessed by hybridization kinetic analysis. All 3 genes are present at 1 copy each per haploid genome in normal tissues and myelomas producing IgM or IgG3. IgG1-producing myelomas, however, contain 1 copy each of the .gamma.1 and .gamma.2a genes and 0.5 copy of the .gamma.3 gene per haploid genome. IgG2b-producing myelomas contain 1 copy of the .gamma.2a gene and 0.5 copy each of the .gamma.1 and .gamma.3 genes per haploid genome. IgG2a-producing myelomas contain 1 copy of the .gamma.2a gene and 0.5 copy each of the .gamma.1 and .gamma.3 genes per haploid genome. In myelomas producing IgA, all 3 .gamma. genes are represented 0.5 time per haploid genome. In order to account for the results an allelic deletion model is proposed: the specific deletion of heavy chain constant region genes accompanies the recombination of a variable region gene to a constant region gene; the portion of the chromosome that resides between 2 joining sequences is excised out of the chromosome; the recombination occurs on 1 of the alleles. Heavy chain genes are arranged on 1 chromosome in the following order; variable region genes, unknown spacer sequence, .mu., .gamma.3, .gamma.1, .gamma.2b, .gamma.2a and .alpha.