Role of OCA-B in 3'-IgH enhancer function.
OCA-B (alternately called Bob1 and OBF-1) is a B cell-specific coactivator that interacts with the ubiquitously expressed Oct-1 and the B cell-restricted Oct-2 to activate transcription via the octamer site (5'-ATGCAAAT-3'). OCA-B-/- mice appear to undergo normal Ag-independent B cell maturation. However, Ag-dependent B cell differentiation, including germinal center formation, production of secondary Ig isotypes, and proliferation in response to surface Ig cross-linking, is greatly affected. We demonstrate that the observed reductions in expression of class-switched isotypes in OCA-B-/- mice may be due in part to deficiencies in the function of the 3'-IgH enhancer elements. Furthermore, we find that surface Ig cross-linking represses all the Ig enhancers and that this repression is absent in OCA-B-/- B cells. These results suggest an important role for OCA-B in Ig enhancer function in vivo.
Stevens
S
S
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10021, USA.
Ong
J
J
Kim
U
U
Eckhardt
L A
LA
Roeder
R G
RG
D020413:3' Untranslated Regions / Q000276:immunology*; D016475:3T3 Cells; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004357:Drug Synergism; D004742:Enhancer Elements, Genetic / Q000276:immunology*; D007106:Immune Sera / Q000494:pharmacology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D007438:Introns / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D020413:3' Untranslated Regions; D019013:CD40 Antigens; D007106:Immune Sera; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; C490424:Pou2af1 protein, mouse; D011947:Receptors, Antigen, B-Cell; D015534:Trans-Activators; D015847:Interleukin-4