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PMID: 9724642 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

OCA-B integrates B cell antigen receptor-, CD40L- and IL 4-mediated signals for the germinal center pathway of B cell development.

The EMBO journal ·Vol. 17 ·No. 17 ·1998-09-01 ·Pages 5066-75

Qin XF, Reichlin A, Luo Y, Roeder RG, Nussenzweig MC

Abstract

Many of the key decisions in lymphocyte differentiation and activation are dependent on integration of antigen receptor and co-receptor signals. Although there is significant understanding of these receptors and their signaling pathways, little is known about the molecular requirements for signal integration at the level of activation of gene expression. Here we show that in primary B cells, expression of the B-cell specific transcription coactivator OCA-B (also known as OBF-1 or Bob-1) is regulated synergistically by the B-cell antigen receptor, CD40L and interleukin signaling pathways. Consistent with the requirement for multiple T cell-dependent signals to induce OCA-B, we find that OCA-B protein is highly expressed in germinal center B cells. Accordingly, germinal center formation is blocked completely in the absence of OCA-B expression in B cells, whereas the helper functions of OCA-B-deficient T cells are indistinguishable from controls. The requirement for OCA-B expression in B cells is germinal center specific since the development of primary B cell follicles, the marginal zone and plasma cells are all intact. Thus, OCA-B is the first example of a transcriptional coactivator that is both synergistically induced by and required for integration of signals that mediate cell fate decisions.

MeSH Terms
Adoptive Transfer Animals B-Cell Lymphoma 3 Protein B-Lymphocytes/cytology,immunology,metabolism CD40 Ligand Carrier Proteins Cell Differentiation DNA-Binding Proteins Gene Expression Regulation Germinal Center/cytology,immunology,metabolism Immunoglobulin Isotypes/biosynthesis Membrane Glycoproteins/metabolism Mice Mice, Inbred C57BL Mice, Knockout Octamer Transcription Factor-2 Oncogene Proteins v-abl/metabolism Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-6 Receptors, Antigen, B-Cell/metabolism Receptors, Cell Surface/metabolism Receptors, Interleukin-4/metabolism Signal Transduction Spleen/cytology,immunology,metabolism Trans-Activators/biosynthesis Transcription Factors
Chemicals
B-Cell Lymphoma 3 Protein Bcl3 protein, mouse Carrier Proteins DNA-Binding Proteins Immunoglobulin Isotypes Membrane Glycoproteins Octamer Transcription Factor-2 Oncogene Proteins v-abl Pou2af1 protein, mouse Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-6 Receptors, Antigen, B-Cell Receptors, Cell Surface Receptors, Interleukin-4 Trans-Activators Transcription Factors CD40 Ligand
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Qin X F
Laboratory of Molecular Immunology, 1230 York Avenue, New York, NY 10021, USA.
Reichlin A
Luo Y
Roeder R G
Nussenzweig M C
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/17.17.5066
Published
1998-09-01
Pages
5066-75
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1170834
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/17.17.5066 PMC Full Text View journal details
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