Nuclear factor kappa B is required for the development of marginal zone B lymphocytes

Although immunoglobulin (Ig)M(hi)IgD(lo/-)CD21(hi) marginal zone B cells re present a significant proportion of naive peripheral splenic B lymphocytes, few of the genes that regulate their development have been identified. Thi s subset of peripheral B cells fails to emerge in mice that lack nuclear fa ctor (NF)-kappa Bp50. Less drastic reductions in marginal zone B cell. numb ers are also seen in the spleens of recombination activating gene (Rag)-2(- /-) mice reconstituted with NF-kappa Bp65(-/-) fetal liver cells and in c-R el(-/-) mice. In contrast, steady-state levels of IgD(hi) splenic follicula r B cells are not significantly reduced in the absence of NF-kappa Bp50, NF -kappa Bp65, or c-Rel. Reconstitution of B cells in Rag-2(-/-) mice with a mixture of p50(-/-)/p65(-/-) fetal liver cells and Rag-2(-/-) bone marrow c ells revealed that the generation of marginal zone B cells requires the exp ression of NF-kappaB in developing B cells, as opposed to supporting cells.