COMPARTMENTALIZATION OF LAMBDA-SUBTYPE EXPRESSION IN THE B-CELL REPERTOIRE OF MICE WITH A DISRUPTED OR NORMAL C-KAPPA GENE SEGMENT

The establishment of the B cell repertoire depends on two major parame ters. The first is determined by mechanistic processes that give rise to a great diversity of B cell receptors from a combination of multipl e gene segments. The second is dominated by selective processes that r ecruit B cell clones via their Immunoglobulin receptors. To assess the impact of these parameters on the composition of B cell repertoire, w e constructed a mouse model displaying a B cell repertoire limited in its diversity. To this end, we disrupted the C(kappa) segment by gene targeting. B cells from such mutant mice do not express the kappa ligh t chain. Their light chain repertoire is therefore limited by the expr ession of only four main lambda light chains: lambda1, lambda2(V2), la mbda2(Vx) and lambda3. In this study we described the proportions of e ach lambda subtype in various lymphoid compartments. Our results show that the lambda1 subtype is dominant in the spleen and the bone marrow . Moreover, lambda1 prevalence is independent of the wild or mutant C( kappa) genotype. These results suggest that the mechanistic processes are mainly responsible for the blas in lambda subtype expression. On t he other hand, the lambda2(V2) and/or lambda3 subtypes are expressed a t higher levels in the peritoneal cavity. Their prevalence is again ob served regardless of the C(kappa) genotype and seems to be due to B1 c ells. These results suggest that different mechanistic processes could control lambda subtype expression in B1 and B2 cell lineages.