Nuclear Factor κb Is Required for the Development of Marginal Zone B Lymphocytes

Although immunoglobulin (Ig)M^hiIgD^lo/−CD21^hi marginal zone B cells represent a significant proportion of naive peripheral splenic B lymphocytes, few of the genes that regulate their development have been identified. This subset of peripheral B cells fails to emerge in mice that lack nuclear factor (NF)-κBp50. Less drastic reductions in marginal zone B cell numbers are also seen in the spleens of recombination activating gene (Rag)-2^−/− mice reconstituted with NF-κBp65^−/− fetal liver cells and in c-Rel^−/− mice. In contrast, steady-state levels of IgD^hi splenic follicular B cells are not significantly reduced in the absence of NF-κBp50, NF-κBp65, 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 cells revealed that the generation of marginal zone B cells requires the expression of NF-κB in developing B cells, as opposed to supporting cells.