Critical roles for the Bcl-3 oncoprotein in T cell-mediated immunity, splenic microarchitecture, and germinal center reactions.
Chromosomal translocations of bcl-3 are associated with chronic B cell lymphocytic leukemias. Previously, we have shown that Bcl-3, a distinct member of the I kappa B family, may function as a positive regulator of NF-kappa B activity, although its physiologic roles remained unknown. To uncover these roles, we generated Bcl-3-deficient mice. Mutant mice, but not their littermate controls, succumb to T. gondii owing to failure to mount a protective T helper 1 immune response. Bcl-3-deficient mice are also impaired in germinal center reactions and T-dependent antibody responses to influenza virus. The results reveal critical roles for Bcl-3 in antigen-specific priming of T and B cells. Altered microarchitecture of secondary lymphoid organs in mutant mice, including partial loss of B cells, may underlie the immunologic defects. The implied role of Bcl-3 in maintaining B cells in wild-type mice may related to its oncogenic potential.
Franzoso
G
G
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland-20892, USA.
Carlson
L
L
Scharton-Kersten
T
T
Shores
E W
EW
Epstein
S
S
Grinberg
A
A
Tran
T
T
Shacter
E
E
Leonardi
A
A
Anver
M
M
Love
P
P
Sher
A
A
Siebenlist
U
U
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000081242:B-Cell Lymphoma 3 Protein; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D004622:Embryo, Mammalian; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D007111:Immunity, Cellular / Q000235:genetics; D009980:Influenza A virus / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D011519:Proto-Oncogenes / Q000276:immunology; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D013234:Stem Cells; D013601:T-Lymphocytes / Q000276:immunology*; D014123:Toxoplasmosis / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors
D000914:Antibodies, Viral; D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors