The 3' enhancer region determines the B/T specificity and pro-B/pre-B specificity of immunoglobulin V kappa-J kappa joining.
Using transgenic substrates, we found that the immunoglobulin kappa gene 3' enhancer (E3') acts as a negative regulator in V kappa-J kappa joining. Although the E3' was originally identified as a transcriptional enhancer, it acts in a suppressive manner for recombinational regulation. Base substitution analysis has shown that the PU.1-binding site within the E3' regulates the B/T specificity of V kappa-J kappa joining. 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.
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA.
R
R
Hiramatsu
K
K
Akagi
M
M
Matsuoka
K
K
Sakumi
H
H
Nakamura
L
L
Kingsbury
C
C
David
R R
RR
Hardy
K
K
Yamamura
H
H
Sakano
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D004742:Enhancer Elements, Genetic / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D007133:Immunoglobulin Joining Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011995:Recombination, Genetic / Q000276:immunology; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D013489:Suppression, Genetic / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic / Q000235:genetics
D007133:Immunoglobulin Joining Region; D007145:Immunoglobulin kappa-Chains