B-cell-specific coactivator OBF-1/OCA-B/Bob1 required for immune response and germinal centre formation

• Published in: Nature (London) 1996-10, Vol.383 (6600), p.538-541
• Main Authors: SCHUBART, D. B, ROLINK, A, KOSCO-VILBOIS, M. H, BOTTERI, F, MATTHIAS, P
• Format: Article
• Language: English
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Antibody Formation - physiology; Antibody production; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Biological and medical sciences; Bone Marrow Cells; Cell differentiation; Cell Differentiation - genetics; Cell Differentiation - physiology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Targeting; Genes; Germinal Center - cytology; Germinal Center - immunology; Immune response; Immunity (Disease); Immunity - physiology; Immunization; Immunobiology; Immunoglobulin A - blood; Immunoglobulin G - blood; Lymphocytes; Mice; Mice, Inbred C57BL; Molecular biology; Mutagenesis; Rodents; Spleen - cytology; Stem cells; Trans-Activators - genetics; Trans-Activators - physiology
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/383538a0

The B-lymphocyte-specific transcriptional factor called Oct binding factor (OBF)-1, OCA-B or Bob1 (refs 1-3) is thought to be involved in the transcription of immunoglobulin genes through recruitment to the highly conserved octamer site of immunoglobulin promoters, mediated by either Oct-1 or Oct-2. To define the in vivo role of OBF-1 we have used gene targeting in embryonic stem cells to generate mice lacking the coactivator OBF-1. Such OBF-1-/- mice are born normally, are fertile and seem healthy, and surprisingly, rearrangement and transcription of immunoglobulin genes are largely unaffected. However, mice deficient in OBF-1 have reduced numbers of mature B cells and a severe reduction in the number of recirculating B cells, but otherwise show normal B-cell differentiation. Serum IgA and particularly IgG levels are greatly reduced. If mutant mice are immunized with either a thymus-independent or a thymus-dependent antigen, their immune responses are dramatically weakened. Strikingly, germinal centres completely fail to develop after immunization with thymus-dependent antigen. Our results demonstrate that in vivo OBF-1 is not required for initial transcription of immunoglobulin genes or for B cell development, but instead is essential for the response of B cells to antigens, and is required for the formation of germinal centres.