Cell-Specific Association and Shuttling of IκBα Provides a Mechanism for Nuclear NF-κB in B Lymphocytes

ABSTRACT 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 viability in several genetically altered mouse strains. Here we suggest a mechanism for the cell specificity and the subunit composition of constitutive B-cell NF-κB based on the observed properties of Rel homo- and heterodimers and IκBα. We show that c-Rel lacks a nuclear export sequence, making the removal of c-Rel-containing complexes from the nucleus less efficient than removal of p65-containing complexes. Second, the nuclear import potential of p65 and c-Rel homodimers but not p50-associated heterodimers was attenuated when they were complexed to IκBα, leading to a greater propensity of heterodimers to be nuclear. We propose that subunit composition of B-cell NF-κB reflects the inefficient retrieval of p50–c-Rel heterodimers from the nucleus. Cell specificity may be a consequence of c-Rel–IκBα complexes being present only in mature B cells, which leads to nuclear c-Rel due to IκBα turnover and shuttling of the complex.

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