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 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-beta 2 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.
Poljak
L
L
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Carlson
L
L
Cunningham
K
K
Kosco-Vilbois
M H
MH
Siebenlist
U
U
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000502:physiology*; D019264:Adoptive Transfer; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D000081242:B-Cell Lymphoma 3 Protein; D001485:Basement Membrane / Q000276:immunology / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics; D020566:Dendritic Cells, Follicular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology* / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D052002:NF-kappa B p50 Subunit; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000276:immunology
D000276:Adjuvants, Immunologic; D000936:Antigen-Antibody Complex; D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors