Mark McAlister
Summer Research Description: The humoral immune response is important for the production of immunological memory towards foreign pathogens. Recent studies reveal that cellular metabolism is intimately connected to the function of lymphocytes. In addition, a previous study from our lab shows that mTORC2 signaling, an integrator of cell signaling pathways and metabolic cues, is important for the survival and maturation of B cells. SGK1, serum- and glucocorticoid-induced protein kinase 1, is shown to be a downstream effecter molecule in the mTORC2 signaling pathway; however, the role of SGK1 signaling in B cells remains unknown. We hypothesize that SGK1 signaling plays a role in B cell responses similar to the role of mTORC2 signaling in B cell homeostasis. To address this hypothesis we inhibited SGK1 signaling in lipopolysaccharide (LPS) activated B cells using GSK-650394, a drug that inhibits the function of SGK1, in the presence of cytokines, IL4 and IFNg, which are important for the initiation of class-switch recombination. Next, we assessed B cell function by measuring the frequency of class switched B cells through flow cytometry and ELISA, which measures antibody secretion in cell culture supernatants. This work will further elucidate the role of mTORC2 signaling in B cell responses.