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B Required for Proper Secondary Lymphoid Organ Microarchitecture: Functions Enhanced by Bcl-3

*
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and
Serono Pharmaceutical Research Institute, Plan-les-Ouates, Geneva, Switzerland
Mice rendered deficient in p52, a subunit of NF-
B, or in Bcl-3,
an I
B-related regulator that associates with p52 homodimers, share
defects in the microarchitecture of secondary lymphoid organs. The
mutant mice are impaired in formation of B cell follicles and are
unable to form proper follicular dendritic cell (FDC) networks upon
antigenic challenge. The defects in formation of B cell follicles may
be attributed, at least in part, to impaired production of the B
lymphocyte chemoattractant (BLC) chemokine, possibly a result of
defective FDCs. The p52- and Bcl-3-deficient mice exhibit additional
defects within the splenic marginal zone, including reduced numbers of
metallophilic macrophages, reduced deposition of the laminin-ß2 chain
and impaired expression of a mucosal addressin marker on sinus-lining
cells. Whereas p52-deficient mice are severely defective in all of
these aspects, Bcl-3-deficient mice are only partially defective. We
determined that FDCs or other non-hemopoietic cells that underlie FDCs
are intrinsically impaired in p52-deficient mice. Adoptive transfers of
wild-type bone marrow into p52-deficient mice failed to restore FDC
networks or follicles. The transfers did restore metallophilic
macrophages to the marginal zone, however. Together, the results
suggest that p52 carries out functions essential for a proper splenic
microarchitecture in both hemopoietic and non-hemopoietic cells and
that Bcl-3 is important in enhancing these essential activities of
p52.
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