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 duri ng 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. I n the present study, precursor B lymphocytes were engineered to expres s 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 Igh transcription and rearrangement, whereas recombinase activity was unaffected. These findings suggest that c-Rel and RelA serve compensa tory functional roles in the developmental mechanisms that govern Ig k appa gene assembly.