B-cell-specific coactivator OBF-1/OCA-B/Bob1 required for immune response and germinal centre formation.
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.
Schubart
D B
DB
Friedrich Miescher Institute, Basel, Switzerland.
Rolink
A
A
Kosco-Vilbois
M H
MH
Botteri
F
F
Matthias
P
P
D000818:Animals; D000917:Antibody Formation / Q000502:physiology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D018390:Gene Targeting; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology; D007109:Immunity / Q000502:physiology*; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D013154:Spleen / Q000166:cytology; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
D007070:Immunoglobulin A; D007074:Immunoglobulin G; C490424:Pou2af1 protein, mouse; D015534:Trans-Activators