Targeted disruption of the p50 subunit of NF-kappa B leads to multifocal defects in immune responses.
NF-kappa B, a heterodimeric transcription factor composed of p50 and p65 subunits, can be activated in many cell types and is thought to regulate a wide variety of genes involved in immune function and development. Mice lacking the p50 subunit of NF-kappa B show no developmental abnormalities, but exhibit multifocal defects in immune responses involving B lymphocytes and nonspecific responses to infection. B cells do not proliferate in response to bacterial lipopolysaccharide and are defective in basal and specific antibody production. Mice lacking p50 are unable effectively to clear L. monocytogenes and are more susceptible to infection with S. pneumoniae, but are more resistant to infection with murine encephalomyocarditis virus. These data support the role of NF-kappa B as a vital transcription factor for both specific and nonspecific immune responses, but do not indicate a developmental role for the factor.
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Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Liou
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Tuomanen
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Baltimore
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D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015152:Blotting, Northern; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D007132:Immunoglobulin Isotypes / Q000032:analysis / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D046911:Macromolecular Substances; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D016328:NF-kappa B / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger / Q000032:analysis; D013290:Streptococcal Infections / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism
D016207:Cytokines; D007132:Immunoglobulin Isotypes; D008070:Lipopolysaccharides; D046911:Macromolecular Substances; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D012333:RNA, Messenger; D014157:Transcription Factors; D016899:Interferon-beta