期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 200, 期 9, 页码 1205-1211出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20041135
关键词
B cell development; V(D)J recombination; accessibility; monospecificity; transcription factor
资金
- NIAID NIH HHS [R01 AI044838, AI44838] Funding Source: Medline
The immunoglobulin Knight chain intronic enhancer (iE(kappa)) activates K rearrangement and is required to maintain the earlier or more efficient rearrangement of K versus lambda (X). To understand the mechanism of how iE(kappa) regulates K rearrangement, we employed homologous recombination to mutate individual functional motifs within iE(kappa) in the endogenous K locus, including the NF-kappaB binding site (kappaB), as well as kappaE1, kappaE2, and kappaE3 E boxes. Analysis of the impacts of these mutations revealed that kappaE2 and to a lesser extent kappaE1, but not kappaE3, were important for activating K rearrangement. Surprisingly, mutation of the kappaB site had no apparent effect on K rearrangement. Comparable to the deletion of the entire iE(kappa), simultaneous mutation of kappaE1 and kappaE2 reduces the efficiency of K rearrangement much more dramatically than either kappaE1 or kappaE2 mutation alone. Because E2A family proteins are the only known factors that bind to these E boxes, these findings provide unambiguous evidence that E2A is a key regulator of kappa rearrangement.
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