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The Journal of Immunology, 2004, 173: 1158-1165.
Copyright © 2004 by The American Association of Immunologists

Direct Repression of prdm1 by Bcl-6 Inhibits Plasmacytic Differentiation1

Chainarong Tunyaplin*, A. L. Shaffer{dagger}, Cristina D. Angelin-Duclos2,*, Xin Yu{dagger}, Louis M. Staudt{dagger} and Kathryn L. Calame3,*

* Departments of Microbiology and Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, New York, NY 10032; and {dagger} Metabolism Branch, Division of Clinical Sciences, National Cancer Institute, Bethesda, MD 20892

We have identified two intronic regions of mouse prdm1, the gene encoding B lymphocyte-induced maturation protein-1 (Blimp-1), which confer transcriptional repression in response to Bcl-6. The Bcl-6 response element in intron 5, which is conserved between mice and humans, was studied in detail. It binds Bcl-6 in vitro and was shown by chromatin immunoprecipitation to be occupied by Bcl-6 in vivo. Neither Bcl-6 response element functions as a STAT3-response element, showing that STAT3 does not compete with Bcl-6 at these sites. Bcl-6–/– mice confirm the biological importance of Bcl-6-dependent repression of prdm1. These mice have elevated Ab response, increased Ig-secreting cells, and increased Blimp-1+ cells in spleen following immunization and their splenic B cells show accelerated plasmacytic development in vitro.




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