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Regulation of 3' IgH enhancers by a common set of factors, including κB-binding proteins

Michaelson, Jennifer S. and Singh, Mallika and Snapper, Clifford M. and Sha, William C. and Baltimore, David and Birshtein, Barbara K. (1996) Regulation of 3' IgH enhancers by a common set of factors, including κB-binding proteins. Journal of Immunology, 156 (8). pp. 2828-2839. ISSN 0022-1767.

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Targeted disruption of the p50 subunit of NF-κB resulted in isotype class switch defects resembling those observed in mice in which the downstream IgH enhancer 3'αE(hs1,2) was deleted. We postulated that κ B binding proteins may regulate class switching by interacting with 3'αE(hs1,2) or with other IgH 3' enhancers with which 3'αE(hs1,2) synergizes. κB binding sites were identified in 3'αE(hs1,2) and 3' αhs4, the distal 3' IgH enhancer. A κB binding site within 3'αE(hs1,2) contributes to at least half the activity of the enhancer in plasma cells, while the same κB binding site participates in the complex repression of the enhancer in B cells. In the case of 3'α-hs4, a κB binding complex activates the enhancer in pre-B, B cells and plasma cells. Additional binding sites within 3'α-hs4 for factors known to regulate 3'αE(hs1,2), including Oct-1 and BSAP, were identified, and their contribution to 3'α-hs4 regulation during B cell development was assessed. Oct-1 positively regulates the enhancer in pre-B and B cells, while BSAP is a repressor in pre-B cells and an activator at the B cell stage. These studies identify κB binding proteins as key modulators of 3'αE(hs1,2) and 3'α-hs4, and suggest coregulation of the two enhancers by a common set of factors.

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Baltimore, David0000-0001-8723-8190
Additional Information:© 1996 by The American Association of Immunologists. Received for publication October 4, 1995. Accepted for publication February 9, 1996. This work was supported by National Institutes of Health (NIH) Grants A113509 and PC30CA13330 (to B.K.B), and GM39458 (to D.B.J. W.C.S. was supported by Fellowship Al08724 from the NIH. J.S.M. was supported by Howard Hughes Medical Institute Predoctoral Fellowship 9-526-4653. The data in this paper are from a thesis that was submitted by J.S.M. in partial fulfillment of the requirements for the of Doctor of Philosophy in the Sue Golding Division of Medical Sciences, Einstein College of Medicine, Yeshiva University. This work was also supported by the Amgen Corporation (D.B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Howard Hughes Medical Institute (HHMI)9-526-4653
Issue or Number:8
Record Number:CaltechAUTHORS:20200507-133625002
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Official Citation:Regulation of 3' IgH enhancers by a common set of factors, including kappa B-binding proteins. J S Michaelson, M Singh, C M Snapper, W C Sha, D Baltimore, B K Birshtein. The Journal of Immunology April 15, 1996, 156 (8) 2828-2839.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103077
Deposited By: Tony Diaz
Deposited On:08 May 2020 17:48
Last Modified:08 May 2020 17:48

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