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B Kinase 
Is Critical for B Cell Proliferation and Antibody Response
Division of Hematology-Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390
The NF-
B proteins are critical in the regulation of the immune
and inflammatory response. Stimulation of the NF-B pathway leads to
increases in I-B kinase 
(IKK) kinase activity to result in
the enhanced phosphorylation and degradation of I-B and the
translocation of the NF-B proteins from the cytoplasm to the
nucleus. In this study, a dominant-negative IKK mutant expressed
from the IgH promoter was used to generate transgenic mice to address
the role of IKK on B cell function. Although these transgenic mice
were defective in activating the NF-B 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 IKK is
critical for the proliferation of B cells and the control of some
aspects of the humoral response.
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