Abstract
OcaB, also known as Bob-1 or Obf-1, is a transcriptional co-activator which regulates Igkappa gene transcription, recombination and receptor editing; it is required for normal development of transitional B cells and for germinal center formation. Here we report that abnormal B cell development in OcaB(-/-) mice results in a skewed Igkappa repertoire including anti-DNA antibodies, suggesting that OcaB is essential for antibody repertoire selection. To determine whether OcaB is required for BCR-mediated B cell selection, we introduced a pre-recombined alpha hen egg lysozyme (HEL) Ig transgene into OcaB(-/-) mice. We find that in OcaB(-/-) mice expressing transgenic alphaHEL Ig bone marrow B cell development is normal up to the immature B cell stage, but fails to progress to the transitional B cell stage. We conclude that OcaB is required for normal selection of the antibody repertoire in developing B cells.
MeSH terms
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Animals
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Antibodies, Antinuclear / blood
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Antibodies, Monoclonal
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Autoantibodies / blood
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B-Lymphocytes / immunology*
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Bone Marrow Cells / immunology
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Cell Cycle
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Cells, Cultured
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Enzyme-Linked Immunosorbent Assay
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Flow Cytometry
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Gene Expression Regulation
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Genes, Immunoglobulin*
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Immune Tolerance
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Immunoglobulin M / biosynthesis
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Immunoglobulin kappa-Chains / biosynthesis
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Immunoglobulin kappa-Chains / genetics
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Immunoglobulins / biosynthesis*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Muramidase / genetics
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Muramidase / immunology
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Polymerase Chain Reaction
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Receptors, Antigen, B-Cell / immunology
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Spleen / cytology
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Trans-Activators / genetics
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Trans-Activators / physiology*
Substances
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Antibodies, Antinuclear
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Antibodies, Monoclonal
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Autoantibodies
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Immunoglobulin M
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Immunoglobulin kappa-Chains
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Immunoglobulins
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Pou2af1 protein, mouse
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Receptors, Antigen, B-Cell
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Trans-Activators
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hen egg lysozyme
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Muramidase