Distinct activities of p52/NF-kappa B required for proper secondary lymphoid organ microarchitecture: Functions enhanced by Bcl-3

Mice rendered deficient in p52, a subunit of NF-kappa B, or in Bcl-3, an I kappa B-related regulator that associates with p52 homodimers, share defect s in the microarchitecture of secondary lymphoid organs. The mutant mice ar e impaired in formation of B cell follicles and are unable to form proper f ollicular dendritic cell (FDC) networks upon antigenic challenge. The defec ts in formation of B cell follicles may be attributed, at least in part, to impaired production of the B lymphocyte chemoattractant (BLC) chemokine, p ossibly a result of defective FDCs, The p52- and Bcl-3-deficient mice exhib it additional defects within the splenic marginal zone, including reduced n umbers of metallophilic macrophages, reduced deposition of the laminin-beta 2 chain and impaired expression of a mucosal addressin marker on sinus-lin ing cells. Whereas p52-deficient mice are severely defective in all of thes e aspects, Bcl-3-deficient mice are only partially defective. We determined that FDCs or other non-hemopoietic cells that underlie FDCs are intrinsica lly impaired in p52-deficient mice. Adoptive transfers of wild-type bone ma rrow into p52-deficient mice failed to restore FDC networks or follicles. T he transfers did restore metallophilic macrophages to the marginal zone, ho wever. Together, the results suggest that p52 carries out functions essenti al for a proper splenic microarchitecture in both hemopoietic and non-hemop oietic cells and that Bcl-3 is important in enhancing these essential activ ities of p52.