Immunological defects in mice with a targeted disruption in Bcl-3.
The proto-oncogene bcl-3 is a member of the IkappaB family. The Bcl-3 protein is known to interact specifically with the p50 and p52 subunits of NFkappaB. However, the function of this interaction is not well understood. To determine the in vivo role of Bcl-3, mice were generated that lack the bcl-3 gene, Bcl 3(-/-). Here we report that Bcl 3(-/-) mice appear developmentally normal, but exhibit severe defects in humoral immune responses and protection from in vivo pathogenic challenges. Relative to wild-type mice, Bcl 3(-/-) mice are unable to clear L. monocytogenes and are more susceptible to infection with S. pneumoniae. This phenotype is similar to that observed in the p50(-/-) mice and the cross between the Bcl-3(-/-) and p50(-/-) mice generates animals with an enhanced phenotype. In accordance with the observed defects in their immune response, the Bcl 3(-/-) mice have normal immunoglobulin levels before and after immunization, but fail to produce antigen-specific antibodies. Additionally, spleens from Bcl-3(-/-) mice are abnormal and void of germinal centers. In contrast, the p50(-/-) mice have normal germinal centers. We propose that in in vivo, Bcl-3 can function independently of p50.
Schwarz
E M
EM
Laboratory of Genetics, The Salk Institute, San Diego, California 92186-5800, USA.
Krimpenfort
P
P
Berns
A
A
Verma
I M
IM
D000818:Animals; D000917:Antibody Formation; D000081242:B-Cell Lymphoma 3 Protein; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology; D018188:Cardiovirus Infections / Q000276:immunology; D004686:Encephalomyocarditis virus; D005260:Female; D015870:Gene Expression; D018390:Gene Targeting; D018858:Germinal Center / Q000276:immunology*; D007113:Immunity, Innate; D007121:Immunocompetence; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D051841:Transcription Factor RelB; D014157:Transcription Factors
D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497594:Relb protein, mouse; D014157:Transcription Factors; D051841:Transcription Factor RelB