The nfkb2 gene is a member of the Rel/NF-κB 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-κB2, we have generated mutant mice carrying a germline mutation of the nfkb2 gene by homologous recombination. NF-κB2–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-κB2–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-κB2 in the maintenance of the peripheral B cell population, humoral responses, and normal spleen architecture.
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19 January 1998
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January 19 1998
Nuclear Factor (NF)-κB2 (p100/p52) Is Required for Normal Splenic Microarchitecture and B Cell–mediated Immune Responses
Jorge H. Caamaño,
Jorge H. Caamaño
From the *Department of Oncology and the ‡Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000; and the §Department of Pathology, Uniformed Services, University of Health Sciences, Bethesda, Maryland 20814
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Cheryl A. Rizzo,
Cheryl A. Rizzo
From the *Department of Oncology and the ‡Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000; and the §Department of Pathology, Uniformed Services, University of Health Sciences, Bethesda, Maryland 20814
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Stephen K. Durham,
Stephen K. Durham
From the *Department of Oncology and the ‡Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000; and the §Department of Pathology, Uniformed Services, University of Health Sciences, Bethesda, Maryland 20814
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Debra S. Barton,
Debra S. Barton
From the *Department of Oncology and the ‡Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000; and the §Department of Pathology, Uniformed Services, University of Health Sciences, Bethesda, Maryland 20814
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Carmen Raventós-Suárez,
Carmen Raventós-Suárez
From the *Department of Oncology and the ‡Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000; and the §Department of Pathology, Uniformed Services, University of Health Sciences, Bethesda, Maryland 20814
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Clifford M. Snapper,
Clifford M. Snapper
From the *Department of Oncology and the ‡Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000; and the §Department of Pathology, Uniformed Services, University of Health Sciences, Bethesda, Maryland 20814
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Rodrigo Bravo
Rodrigo Bravo
From the *Department of Oncology and the ‡Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000; and the §Department of Pathology, Uniformed Services, University of Health Sciences, Bethesda, Maryland 20814
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Jorge H. Caamaño
From the *Department of Oncology and the ‡Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000; and the §Department of Pathology, Uniformed Services, University of Health Sciences, Bethesda, Maryland 20814
Cheryl A. Rizzo
From the *Department of Oncology and the ‡Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000; and the §Department of Pathology, Uniformed Services, University of Health Sciences, Bethesda, Maryland 20814
Stephen K. Durham
From the *Department of Oncology and the ‡Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000; and the §Department of Pathology, Uniformed Services, University of Health Sciences, Bethesda, Maryland 20814
Debra S. Barton
From the *Department of Oncology and the ‡Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000; and the §Department of Pathology, Uniformed Services, University of Health Sciences, Bethesda, Maryland 20814
Carmen Raventós-Suárez
From the *Department of Oncology and the ‡Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000; and the §Department of Pathology, Uniformed Services, University of Health Sciences, Bethesda, Maryland 20814
Clifford M. Snapper
From the *Department of Oncology and the ‡Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000; and the §Department of Pathology, Uniformed Services, University of Health Sciences, Bethesda, Maryland 20814
Rodrigo Bravo
From the *Department of Oncology and the ‡Department of Experimental Pathology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000; and the §Department of Pathology, Uniformed Services, University of Health Sciences, Bethesda, Maryland 20814
Address correspondence to Rodrigo Bravo, Department of Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, New Jersey 08543-4000. Phone: 609-252-5744; Fax: 609-252-3307; E-mail: bravo#m#[email protected] Jorge H. Caamaño's present address is Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce St., Philadelphia, PA, 19104-6008.
1
Abbreviations used in this paper: EMSA, electrophoretic mobility shift assays; ES, embryonic stem; FDC, follicular dendritic cell; GC, germinal center; PNA, peanut agglutinin; SRBC, sheep red blood cell.
Received:
July 23 1997
Revision Received:
November 14 1997
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 187 (2): 185–196.
Article history
Received:
July 23 1997
Revision Received:
November 14 1997
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Jorge H. Caamaño, Cheryl A. Rizzo, Stephen K. Durham, Debra S. Barton, Carmen Raventós-Suárez, Clifford M. Snapper, Rodrigo Bravo; Nuclear Factor (NF)-κB2 (p100/p52) Is Required for Normal Splenic Microarchitecture and B Cell–mediated Immune Responses . J Exp Med 19 January 1998; 187 (2): 185–196. doi: https://doi.org/10.1084/jem.187.2.185
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