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Mice Deficient in NF-κB/p52 present with defects in humoral responses, germinal center reactions and splenic microarchitecture.

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Title: Mice Deficient in NF-κB/p52 present with defects in humoral responses, germinal center reactions and splenic microarchitecture.
Authors: Franzoso, G
Carlson, L
Poljak, L
Shores, EW
Epstein, S
Leonardi, A
Grinberg, A
Tran, T
Sharton-Kersten, T
Anver, M
Love, P
Brown, K
Siebenlist, U
Item Type: Journal Article
Abstract: p52 is a subunit of nuclear factor (NF)-κB transcription factors, most closely related to p50. Previously, we have shown that p52, but not p50 homodimers can form transactivating complexes when associated with Bcl-3, an unusual member of the IκB family. To determine nonredundant physiologic roles of p52, we generated mice deficient in p52. Null mutant mice were impaired in their ability to generate antibodies to T-dependent antigens, consistent with an absence of B cell follicles and follicular dendritic cell networks in secondary lymphoid organs, and an inability to form germinal centers. Furthermore, the splenic marginal zone was disrupted. These phenotypes are largely overlapping with those observed in Bcl-3 knockout animals, but distinct from those of p50 knockouts, supporting the notion of a physiologically relevant complex of p52 homodimers and Bcl-3. Adoptive transfer experiments further suggest that such a complex may be critical in accessory cell functions during antigen-specific immune reactions. Possible roles of p52 and Bcl-3 are discussed that may underlie the oncogenic potential of these proteins, as evidenced by recurrent chromosomal translocations of their genes in lymphoid tumors.
Issue Date: 1998
Date of Acceptance: 1-Jan-1998
URI: http://hdl.handle.net/10044/1/88536
DOI: 10.1084/jem.187.2.147
ISSN: 0022-1007
Publisher: Rockefeller University Press
Start Page: 147
End Page: 159
Journal / Book Title: Journal of Experimental Medicine
Volume: 187
Issue: 2
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
NF-KAPPA-B
CANDIDATE PROTOONCOGENE BCL-3
DNA-BINDING
ONCOPROTEIN BCL-3
IMMUNE-RESPONSE
P50 HOMODIMERS
LYMPHOID MALIGNANCIES
TARGETED DISRUPTION
DENDRITIC CELLS
PRECURSOR P105
Adoptive Transfer
Animals
Antibody Formation
B-Lymphocyte Subsets
Germinal Center
Immunologic Deficiency Syndromes
Lymphocyte Count
Mice
Mice, Inbred Strains
Mice, Knockout
NF-kappa B
Proto-Oncogene Proteins
Spleen
T-Lymphocyte Subsets
Toxoplasma
Toxoplasmosis, Animal
Germinal Center
Spleen
B-Lymphocyte Subsets
T-Lymphocyte Subsets
Animals
Mice, Inbred Strains
Mice, Knockout
Mice
Toxoplasma
Toxoplasmosis, Animal
Immunologic Deficiency Syndromes
NF-kappa B
Proto-Oncogene Proteins
Lymphocyte Count
Adoptive Transfer
Antibody Formation
Immunology
11 Medical and Health Sciences
Publication Status: Published
Online Publication Date: 1998-01-19
Appears in Collections:Department of Immunology and Inflammation



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