BOTH MULTIORGAN INFLAMMATION AND MYELOID HYPERPLASIA IN RELB-DEFICIENT MICE ARE T-CELL-DEPENDENT

Mite with a targeted disruption of RelB, a member of the Rel/NF-kappa B family of transcription factors, have multifocal, mixed inflammatory cell infiltration in several organs, myeloid hyperplasia, and splenom egaly due to extramedullary hemopoiesis, To elucidate the cellular req uirements for this complex phenotype, we have bred RelB-deficient (Rel B(KO)) animals to two strains of immunodeficient mice, recombinase-act ivating gene-1-deficient (RAG-1(KO), lacking B and T cells), and Nur77 /N10-transgenic mice (Nur77/N10(TG), lacking only T cells), We also ge nerated mutant mice deficient in both RelB and the p50 subunit of NF-k appa B (p50(KO), multiple defects in B cell function), RelB(KO)RAG-1(K O) and RelB(KO)Nur(77)/N10(TG) mice are disease-free, while RelB(KO)p5 0(KO) double-mutant animals develop an even more severe phenotype desp ite the absence of B cells in the inflammatory infiltrates, Thus, both multiorgan inflammation and myeloid hyperplasia in RelB-deficient mic e are T cell dependent, whereas B cells are not crucially involved.