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 language||English (US)|
|Number of pages||12|
|Journal||Journal of Immunology|
|State||Published - Apr 15 1996|
ASJC Scopus subject areas
- Immunology and Allergy