The subunit composition of NF-κB complexes changes during b-cell development

The transcription factor NF-κB, shown to be essential for expression of the immunoglobulin Cκ gene, is a key regulatory component in pre-B to B- cell differentiation. While previous studies have used lymphoid cell line models, here we examine the expression and subunit composition of rel/NF-κB complexes in normal murine pre-B and B lymphocytes. Two major NF-κB complexes are detected in pre-B and B cells. A high mobility complex, found in pre-B (C(b)) and B cells (Cβ) is a homodimer of the NF-κB subunit p50. In pre-B cells, the slower migrating complex (C(a)), which is predominantly cytoplasmic, is largely comprised of p50 and p65, whereas in B cells, a nuclear and cytoplasmic complex (Cα) of identical mobility to C(a) mainly consists of p50 and p75(c-rel). While p50 and p65 levels do not change during pre-B to B-cell differentiation, p75(c-rel) is 5- to 6-fold more abundant in B cells compared to pre-B cells, a finding consistent with the switch in NF- κB subunit usage. During lipopolysaccharide-induced B-cell proliferation, transient up-regulation of both the nuclear p50 homodimer and p75(c-rel) containing complex is mirrored by a concurrent increase in c-rel and p105 but not p65 mRNA expression, a finding consistent with rel-NF-κB expression in B cells being controlled by an autoregulatory mechanism.