NUCLEAR FACTOR (NF)-KAPPA-B2 (P100 P52) IS REQUIRED FOR NORMAL SPLENIC MICROARCHITECTURE AND B-CELL-MEDIATED IMMUNE-RESPONSES/

The nfkb2 gene is a member of the Rel/NF-kappa B family of transcripti on factors. COOH-terminal deletions and rearrangements of this gene ha ve been associated with the development of human cutaneous T cell lymp homas, chronic lymphocytic leukemias, and multiple myelomas. To furthe r investigate the function of NF-kappa B2, we have generated mutant mi ce carrying a germline mutation of the nfkb2 gene by homologous recomb ination. NF-kappa B2-deficient mice showed a marked reduction in the B cell compartment in spleen, bone marrow, and lymph nodes. Moreover, s pleen and lymph nodes of mutant mice presented an altered architecture , characterized by diffuse, irregular B cell areas and the absence of discrete perifollicular marginal and mantle zones; the formation of se condary germinal centers in spleen was also impaired. Proliferation of NF-kappa B2-deficient B cells was moderately reduced in response to l ipopolysaccharide, anti-IgD-dextran, and CD40, but maturation and immu noglobulin switching were normal. However, nfkb2 (-/-) animals present ed a deficient immunological response to T cell-dependent and -indepen dent antigens. These findings indicate an important role of NF-kappa B 2 in the maintenance of the peripheral B cell population, humoral resp onses, and normal spleen architecture.