IGBP1 protects WEHI-231 cells from BCR-mediated apoptosis through the maintenance of PP6 activity and Bcl-xL stability.

The elimination of self-reactive clones through B cell receptor (BCR)-induced apoptosis is a fundamental mechanism for establishing self-tolerance in immature B cells. We previously reported that protein phosphatase 6 (PP6) suppresses BCR-induced apoptosis in the immature B cell line WEHI-231 by maintaining the expression of the anti-apoptotic protein, Bcl-xL. Immunoglobulin-binding protein 1 (IGBP1) interacts with the catalytic subunit of PP6 (PP6c) to regulate its phosphatase activity. In this study, we investigated the role of IGBP1 in BCR-mediated apoptosis. We found that IGBP1 overexpression significantly suppressed anti-IgM-induced apoptosis in WEHI-231 cells, whereas its siRNA-mediated knockdown accelerated cell death. Co-immunoprecipitation and activity assays revealed that BCR stimulation attenuates the IGBP1-PP6c interaction and reduces PP6 phosphatase activity. Importantly, this reduction in PP6 activity was prevented by IGBP1 overexpression and exacerbated by its knockdown. Furthermore, IGBP1 positively regulated Bcl-xL stability following BCR stimulation. Notably, exogenous overexpression of Bcl-xL effectively rescued the enhanced apoptosis observed in IGBP1-knockdown cells. Collectively, our findings demonstrate that IGBP1 protects immature B cells from BCR-induced apoptosis by sustaining the IGBP1-PP6c complex and its phosphatase activity, thereby maintaining the expression of Bcl-xL.