On a regulatory gene controlling the expression of the murine lambda1 light chain.

Abstract

We describe here two alleles, an allele of the lambda1 locus present in the SJL strain (rlambda1lo) and an allele of the lambda1 locus present in the BALB/c strain (rlambda1 +), of a regulatory gene locus which specifically influences the expression of the mouse lambda1 light chain structural gene. The rlambda1 regulatory gene is not linked to either the major histocompatibility complex or to the heavy-chain allogroup but appears to be linked to the lambda1 structural gene locus. In the homozygous state, the present of the rlambda1lo allele results in a 50-fold reduction in the number of lambda1 antigen-sensitive, bone-marrow derived lymphocytes (ASCs) compared to the presence of the rlambda1 + allele. However, those few lambda1ASCs present in rlambda1lo homozygotes can be induced normally to produce lambda1 light chains indistinguishable from those found in rlambda1 + homozygotes. The reduction in lambda1ASC's due to the rlambda1lo allele results both in a reduction in the amount of lambda1 Ig in the serum and also in a large variation in the magnitude of the lambda1 antibody response to alpha(1,3) dextran by individual animals. This variation permits the estimate that, on the average, 50 B cells of anti-alpha(1,3) specificity must be present per animal to permit a measurable response. Surprisingly, the expression of a gene locus regulating lambda1 light chain expression (rlambda1 locus) shows a clear gene dosage effect with rlambda1lo/rlambda1 + heterozygotes having 1/2 the number of lambda1ASCs and 1/2 the amount of serum lambda1 Ig as rlambda1 +/rlambda1 + homozygotes. This fact permits an analysis of the relationship between germ-line v-genes and their individual expression in serum Ig. The rlambda1 locus controls specifically a DNA-level event which occurs in stem cells as they become committed to lambda1 light chain expression. We postulate that the rlambda1 locus represents one of the DNA level recognition sites involved in the translocation event which places the vlambda1 and clambda1 structural genes in a transcriptional unit.