During fiscal year 2011, our goal was to rigorously demonstrate that either Pim2 kinase or mTOR activity were signaling intermediates for p100 (NFκB1) production by tonic BCR signaling. This required us to analyze p100 production in Pim2-deficient B cell treated with rapamycin. However, our efforts were hindered by the non-availability of Pim2-deficient mice from our collaborators at University of Massachusetts Medical Center. Additionally, we examined Mcl-1 expression in response to tonic, or acute, BCR signaling. We found that loss of Mcl-1 protein was accentuated in splenic B cells, treated with a PI3 kinase exhibitor (in the absence of BAFF). These observations suggest that tonic BCR signaling maintains Mcl-1 expression via PI3K. Since BAFF/BAFF-R interactions have also been shown to activate PI3K, Mcl-1 expression may be jointly regulated by BCR- and BAFF-R-initiated PI3K activation.
| Castro, Iris; Wright, Jacqueline A; Damdinsuren, Bazarragchaa et al. (2009) B cell receptor-mediated sustained c-Rel activation facilitates late transitional B cell survival through control of B cell activating factor receptor and NF-kappaB2. J Immunol 182:7729-37 |
| Stadanlick, Jason E; Kaileh, Mary; Karnell, Fredrick G et al. (2008) Tonic B cell antigen receptor signals supply an NF-kappaB substrate for prosurvival BLyS signaling. Nat Immunol 9:1379-87 |
