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

J Immunol. 2000 Jan 1;164(1):18-22. doi: 10.4049/jimmunol.164.1.18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Agammaglobulinemia / enzymology
  • Agammaglobulinemia / genetics*
  • Agammaglobulinemia / immunology
  • Agammaglobulinemia / pathology
  • Animals
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Female
  • Gene Expression Regulation / immunology
  • Gene Expression Regulation, Developmental / immunology
  • Genes, Immunoglobulin
  • Genetic Linkage / immunology
  • Humans
  • Immunoglobulins / biosynthesis
  • Immunoglobulins / blood
  • Lymphoid Tissue / pathology
  • Lymphopenia / enzymology
  • Lymphopenia / genetics*
  • Lymphopenia / immunology
  • Lymphopenia / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Knockout
  • Multigene Family / immunology
  • Phenotype
  • Protein-Tyrosine Kinases / deficiency*
  • Protein-Tyrosine Kinases / genetics
  • Trans-Activators / deficiency*
  • Trans-Activators / genetics
  • X Chromosome / genetics
  • X Chromosome / immunology

Substances

  • Immunoglobulins
  • POU2AF1 protein, human
  • Pou2af1 protein, mouse
  • Trans-Activators
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • Btk protein, mouse