Essential roles of the kappa light chain intronic enhancer and 3' enhancer in kappa rearrangement and demethylation.
The kappa intronic (MiE(kappa)) and 3' (3'E(kappa)) enhancers are both quantitatively important to, but not essential for, immunoglobulin kappa rearrangement. To determine the functional redundancy between these two enhancers, B cells derived from mutant embryonic stem cells--in which both MiE(kappa) and 3'E(kappa) were deleted on both kappa alleles--were analyzed for kappa rearrangement. Our findings indicate that these double-mutant B cells have essentially no kappa rearrangement but do rearrange and express lambda. Therefore, these two kappa enhancers share essential roles in activating V(kappa)J(kappa) rearrangement. Our findings also indicate that the two kappa enhancers play overlapping and distinct roles in the demethylation of kappa in B cells.
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Matthew
M
Section of Molecular Biology, Division of Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0322, USA.
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Frederick W
FW
Baltimore
David
D
Xu
Yang
Y
D024509:3' Flanking Region; D000818:Animals; D001483:Base Sequence; D019175:DNA Methylation; D004742:Enhancer Elements, Genetic / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005803:Genes, Immunoglobulin; D007145:Immunoglobulin kappa-Chains / Q000097:blood / Q000235:genetics / Q000276:immunology*; D007146:Immunoglobulin lambda-Chains / Q000276:immunology; D007438:Introns / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000502:physiology
D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains