Cutting edge: lack of peripheral B cells and severe agammaglobulinemia in mice simultaneously lacking Bruton's tyrosine kinase and the B cell-specific transcriptional coactivator OBF-1.
OBF-1 is a B cell-restricted transcriptional coactivator that is recruited to octamer-containing promoters by interacting with the POU domain of Oct-1 or Oct-2. We have shown earlier that mice lacking OBF-1 were dramatically impaired in their ability to mount humoral immune responses and did not develop germinal centers in the spleen; however, they had a largely normal B cell development in the bone marrow. In this study, we demonstrate that OBF-1-deficient mice also have an early defect in B cell development and show that OBF-1-/- immature B cells are greatly impaired at the transition from the bone marrow to the spleen. In addition, when the OBF-1 mutation is combined to a mutation in the gene encoding Bruton's tyrosine kinase, a striking phenotype is observed. These double-deficient animals lack peripheral B cells and have virtually no serum Igs, thus closely resembling human X chromosome-linked agammaglobulinemia.
Schubart
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DB
Friedrich Miescher-Institute, Basel, Switzerland.
Rolink
A
A
Schubart
K
K
Matthias
P
P
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000201:enzymology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D005803:Genes, Immunoglobulin; D008040:Genetic Linkage / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000097:blood; D008221:Lymphoid Tissue / Q000473:pathology; D008231:Lymphopenia / Q000201:enzymology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D005810:Multigene Family / Q000276:immunology; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics; D014960:X Chromosome / Q000235:genetics / Q000276:immunology
D007136:Immunoglobulins; C091546:POU2AF1 protein, human; C490424:Pou2af1 protein, mouse; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse