OcaB regulates transitional B cell selection.
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.
Jankovic
Mila
M
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021-6399, USA.
Nussenzweig
Michel C
MC
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D002453:Cell Cycle; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D007108:Immune Tolerance; D007075:Immunoglobulin M / Q000096:biosynthesis; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis / Q000235:genetics; D007136:Immunoglobulins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009113:Muramidase / Q000235:genetics / Q000276:immunology; D016133:Polymerase Chain Reaction; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D013154:Spleen / Q000166:cytology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D007136:Immunoglobulins; C490424:Pou2af1 protein, mouse; D011947:Receptors, Antigen, B-Cell; D015534:Trans-Activators; C421864:hen egg lysozyme; D009113:Muramidase