Cell-specific association and shuttling of I kappa B alpha provides a mechanism for nuclear NF-kappa B in B lymphocytes

Mature B lymphocytes are unique in containing nuclear Rel proteins prior to cell stimulation. This activity consists largely of p50-c-Rel heterodimers , and its importance for B-cell function is exemplified by reduced B-cell v iability in several genetically altered mouse strains. Here we suggest a me chanism for the cell specificity and the subunit composition of constitutiv e B-cell NF-KB based on the observed properties of Rel homo- and heterodime rs and I kappaB alpha. We show that c-Rel lacks a nuclear export sequence, making the removal of c-Rel-containing complexes from the nucleus less effi cient than removal of p65-containing complexes. Second, the nuclear import potential of p65 and c-Rel homodimers but not p50-associated heterodimers w as attenuated when they were complexed to I kappaB alpha, leading to a grea ter propensity of heterodimers to be nuclear. We propose that subunit compo sition of B-cell NF-KB reflects the inefficient retrieval of p50-c-Rel hete rodimers from the nucleus. Cell specificity may be a consequence of c-Rel-I kappaB alpha complexes being present only in mature B cells, which leads t o nuclear c-Rel due to I kappaB alpha turnover and shuttling of the complex .