Original Article

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

Correspondence to: Shiv Pillai, Massachusetts General Hospital Cancer Center, Bldg. 149, 13th St., Charlestown, MA 02129. Tel:617-726-5619 Fax:617-724-9648

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)-Bp50. 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-Bp65^-/- 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-Bp50, NF-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 cells revealed that the generation of marginal zone B cells requires the expression of NF-B in developing B cells, as opposed to supporting cells.

Key Words: transcription factors, lymphocyte development, recombination activating gene-2^-/- mice, peripheral B cells, Bruton's tyrosine kinase

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