The B-cell-specific transcription coactivator OCA-B/OBF-1/Bob-1 is essential for normal production of immunoglobulin isotypes.
OCA-B was initially identified as a B-cell-restricted coactivator that functions with octamer binding transcription factors (Oct-1 and Oct-2) to mediate efficient cell type-specific transcription of immunoglobulin promoters in vitro. Subsequent cloning studies led to identification of the coactivator as a single polypeptide, designated either as OCA-B (ref. 3), OBF-1 (ref. 4) or Bob-1 (ref. 5). OCA-B itself does not bind to DNA directly, but interacts with either Oct-1 or Oct-2 to potentiate transcriptional activation. To determine the biological role of OCA-B, we generated OCA-B-deficient mice by gene targeting. Mice lacking OCA-B undergo normal antigen-independent, B-cell differentiation, including appropriate expression of both immunoglobulin genes and other early B-cell-restricted genes. However, antigen-dependent maturation of B cells is greatly affected. The proliferative response to surface IgM crosslinking is impaired, and there is a severe deficiency in the production of secondary immunoglobulin isotypes including IgG1, IgG2a, IgG2b, IgG3, IgA and IgE in OCA-B-deficient B cells. This defect is not due to a failure of the isotype switching process, but rather to reduced levels of transcription from normally switched immunoglobulin heavy-chain loci. In accord with the defective isotype production, germinal centre formation is absent in these mutant mice.
Kim
U
U
Laboratory of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, The Rockefeller University, New York 10021, USA.
Qin
X F
XF
Gong
S
S
Stevens
S
S
Luo
Y
Y
Nussenzweig
M
M
Roeder
R G
RG
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D005434:Flow Cytometry; D018390:Gene Targeting; D005803:Genes, Immunoglobulin; D018858:Germinal Center / Q000166:cytology; D017578:Immunoglobulin Class Switching; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis* / Q000097:blood; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016296:Mutagenesis; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D007132:Immunoglobulin Isotypes; C490424:Pou2af1 protein, mouse; D015534:Trans-Activators