Organization of immunoglobulin heavy chain genes and allelic deletion model

Abstract

We have assessed the number of times the gene sequence encoding constant regions of mouse immunoglobulin heavy chains γ1, γ2a, and γ3 are represented in the mouse genome by hybridization kinetic analysis. All three genes are present at one copy each per haploid genome in normal tissues and myelomas producing IgM or IgG3. IgG1-producing myelomas, however, contain 1 copy each of the γ1 and γ2a genes and 0.5 copy of the γ3 gene per haploid genome. IgG2b producing myelomas contain 1 copy of the γ2a gene and 0.5 copy each of the γ1 and γ3 genes per haploid genome. IgG2a-producing myelomas contain 1 copy of the γ2a gene and 0.5 copy each of the γ1 and γ3 genes per haploid genome. In myelomas producing IgA, all three γ genes are represented 0.5 time per haploid genome. In order to account for the results we propose an allelic deletion model. 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 two rejoining sequences is excised out of the chromosome. The recombination occurs on one of the alleles. Based on this model we also propose that heavy chain genes are arranged on one chromosome in the following order; variable region genes, unknown spacer sequence, μ, γ3, γ1, γ2b, γ2a, and α.