R. Hiramatsu et al., THE 3'-ENHANCER REGION DETERMINES THE B T SPECIFICITY AND PRO-B PRE-BSPECIFICITY OF IMMUNOGLOBULIN-V-KAPPA-J(KAPPA) JOINING/, Cell, 83(7), 1995, pp. 1113-1123
Using transgenic substrates, we found that the immunoglobulin kappa ge
ne 3' enhancer (E3') acts as a negative regulator in V-kappa-J(kappa)
joining. Although the E3' was originally identified as a transcription
al enhancer, it acts in a suppressive manner for recombinational regul
ation. Base substitution analysis has shown that the PU.1-binding site
within the E3' regulates the B/T specificity of V-kappa-J(kappa) join
ing. In a substrate with a mutated PU.1-binding site (GAGGAA to TCTTCG
), V-kappa-J(kappa) joining occurred not only in B cells, but also in
T cells. The E3' region is also responsible for determining the pro-B/
pre-B specificity of V-kappa-J(kappa) joining. When the E3' region was
deleted, kappa gene rearrangement actively occurred at the early pro-
B stage of B cell development: nongermline (N) nucleotides were common
at recombination junctions.