I-κB kinase β is critical for B cell proliferation and antibody response

The NF-κB proteins are critical in the regulation of the immune and inflammatory response. Stimulation of the NF-κB pathway leads to increases in I-κB kinase β (IKKβ) kinase activity to result in the enhanced phosphorylation and degradation of I-κB and the translocation of the NF-κB proteins from the cytoplasm to the nucleus. In this study, a dominant-negative IKKβ mutant expressed from the IgH promoter was used to generate transgenic mice to address the role of IKKβ on B cell function. Although these transgenic mice were defective in activating the NF-κB pathway in B cells, they exhibited no defects in B lymphocyte development or basal Ig levels. However, they exhibited defects in the cell cycle progression and proliferation of B cells in response to treatment with LPS, anti-CD40, and anti-IgM. Furthermore, selective defects in the production of specific Ig subclasses in response to both T-dependent and T-independent Ags were noted. These results suggest that IKKβ is critical for the proliferation of B cells and the control of some aspects of the humoral response.