Bruton's tyrosine kinase targets NF-κB to the bcl-x promoter via a mechanism involving phospholipase C-γ2 following B cell antigen receptor engagement

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Abstract
Disruption of Bruton’s tyrosine kinase (BTK) function leads to x-linked immunodeficiency (xid) in mice. BTK-deficient (btk−/−) B cells are defective for survival. Prior studies show that BTK is required for the induction of Bcl-xL following B cell antigen receptor (BCR) engagement. However, the mechanism underlying Bcl-xL induction in response to BCR ligation remains unresolved. We now demonstrate that BTK regulates bcl-x expression by transcriptional control in response to BCR engagement. BTK targets nuclear factor-κB (NF-κB) to activate the bcl-x promoter via a phospholipase C-γ2 (PLC-γ2)-dependent mechanism. Perturbation of the BTK/PLC-γ2/NF-κB signaling axis likely contributes to the defective expression of bcl-x and compromised survival of xid B cells