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 transcription factors. COOH-terminal deletions and rearrangements of this gene have been associated with the development of human cutaneous T cell lymphomas, chronic lymphocytic leukemias, and multiple myelomas. To further investigate the function of NF-kappa B2, we have generated mutant mice carrying a germline mutation of the nfkb2 gene by homologous recombination. NF-kappa B2-deficient mice showed a marked reduction in the B cell compartment in spleen, bone marrow, and lymph nodes. Moreover, spleen 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 secondary germinal centers in spleen was also impaired. Proliferation of NF-kappa B2-deficient B cells was moderately reduced in response to lipopolysaccharide, anti-IgD-dextran, and CD40, but maturation and immunoglobulin switching were normal. However, nfkb2 (-/-) animals presented a deficient immunological response to T cell-dependent and -independent antigens. These findings indicate an important role of NF-kappa B2 in the maintenance of the peripheral B cell population, humoral responses, and normal spleen architecture.
Caamaño
J H
JH
Department of Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
Rizzo
C A
CA
Durham
S K
SK
Barton
D S
DS
Raventós-Suárez
C
C
Snapper
C M
CM
Bravo
R
R
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D019013:CD40 Antigens / Q000502:physiology; D000939:Epitopes / Q000235:genetics; D005260:Female; D018858:Germinal Center / Q000473:pathology; D007111:Immunity, Cellular / Q000235:genetics; D007136:Immunoglobulins / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D016254:Mutagenesis, Insertional / Q000276:immunology; D016328:NF-kappa B / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D052003:NF-kappa B p52 Subunit; D011947:Receptors, Antigen, B-Cell / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000276:immunology* / Q000473:pathology*
D019013:CD40 Antigens; D000939:Epitopes; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D011947:Receptors, Antigen, B-Cell