Corepression of RelA and c-rel inhibits immunoglobulin kappa gene transcription and rearrangement in precursor B lymphocytes.
Multiple members of the NF-kappa B/Rel protein family are induced during B cell differentiation and have been implicated in transcriptional activation of the immunoglobulin kappa (Ig kappa) locus. Despite these findings, normal numbers of Ig kappa + B lymphocytes are produced by mice bearing targeted mutations in individual NF-kappa B/Rel genes. In the present study, precursor B lymphocytes were engineered to express a trans-dominant form of I kappa B alpha that simultaneously impairs the c-Rel and RelA transactivating subunits of NF-kappa B. This dual block in NF-kappa B/Rel signaling led to potent inhibition of germline Ig kappa transcription and rearrangement, whereas recombinase activity was unaffected. These findings suggest that c-Rel and RelA serve compensatory functional roles in the developmental mechanisms that govern Ig kappa gene assembly.
Scherer
D C
DC
Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville Tennessee 37232, USA.
Brockman
J A
JA
Bendall
H H
HH
Zhang
G M
GM
Ballard
D W
DW
Oltz
E M
EM
D000818:Animals; D001402:B-Lymphocytes; D002478:Cells, Cultured; D004254:DNA Nucleotidyltransferases / Q000032:analysis; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D017930:Genes, Reporter; D005854:Germ Cells; D006412:Hematopoietic Stem Cells; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D019426:Integrases; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020569:Proto-Oncogene Proteins c-rel; D045522:Recombinases; D051996:Transcription Factor RelA; D014158:Transcription, Genetic; D014170:Transformation, Genetic
D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D045522:Recombinases; D051996:Transcription Factor RelA; D004254:DNA Nucleotidyltransferases; D019426:Integrases; C115006:integron integrase IntI1