Overexpression of RelB in transgenic mice does not affect IκBα levels: Differential regulation of RelA and RelB by the inhibitor protein

In mouse lymphoid tissues, RelB heterodimers represent the constitutive κB-binding activity, whereas RelA and c-Rel complexes most likely are involved in inducible κB-binding and gene activation. Our laboratory has previously shown that the potential excess of NF-κB activity in transgenic mice overexpressing RelA is counteracted by a dramatic increase in IκBα, mainly due to its increased stability through association with RelA. As an attempt to elucidate the in vivo mechanisms that lead to the constitutive DNA-binding activity of RelB heterodimers, we have generated mouse lines overexpressing a relB transgene in a position-independent and copy number-dependent manner. Expression of RelB in these transgenic animals is very high in immature thymocytes and restricted to T cell areas in secondary lymphoid tissues. In contrast to the results obtained with RelA-transgenic thymocytes, we demonstrate here that overexpression of RelB results in a dramatic increase in overall κB-binding activity. Interestingly, IκBα protein levels are not altered in the RelB-transgenic animals, indicating that within the same cell type RelA and RelB complexes are differentially regulated by IκBα.