Chromosome choice for initiation of V-(D)-J recombination is not governed by genomic imprinting.

Abstract

V-(D)-J recombination generates the antigen receptor diversity necessary for immune cell function while allelic exclusion ensures that each cell expresses a single antigen-receptor. V-(D)-J recombination of the Ig, Tcrb, Tcrg, and Tcrd antigen receptor genes is ordered and sequential so that only one allele generates a productive rearrangement. The mechanism controlling sequential rearrangement of antigen receptor genes, in particular, how only one allele is selected to initiate recombination while at least temporarily leaving the other intact remains unresolved. Genomic imprinting, a widespread phenomenon wherein maternal or paternal allele inheritance determines allele activity, could represent a regulatory mechanism for controlling sequential V-(D)-J rearrangement. We used strain-specific single nucleotide polymorphisms (SNPs) within antigen receptor genes to determine if maternal vs. paternal inheritance could underlie chromosomal choice for the initiation of recombination. We found no parental chromosomal bias in the initiation of V-(D)-J recombination in T or B cells, eliminating genomic imprinting as a potential regulator for this tightly regulated process.