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

Jennifer S. Michaelson, Mallika Singh, Clifford M. Snapper, William C. Sha, David Baltimore, Barbara K. Birshtein

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

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 κB 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′α-hs4, 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.

Original languageEnglish (US)
Pages (from-to)2828-2839
Number of pages12
JournalJournal of Immunology
Volume156
Issue number8
StatePublished - Apr 15 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Regulation of 3′ IgH enhancers by a common set of factors, including κB-binding proteins'. Together they form a unique fingerprint.

  • Cite this

    Michaelson, J. S., Singh, M., Snapper, C. M., Sha, W. C., Baltimore, D., & Birshtein, B. K. (1996). Regulation of 3′ IgH enhancers by a common set of factors, including κB-binding proteins. Journal of Immunology, 156(8), 2828-2839.