Abstract 805: mTORC protein levels affect class switch recombination, somatic hypermutation, and antibody production

Abstract

Abstract Mammalian target of rapamycin (mTOR) regulates cell growth, cell cycle, and survival through two main complexes, mTORC1 and mTORC2. In our previous studies, striking decreases in both size and number of B cells were seen in mice with constitutive reductions in protein levels of both mTOR complexes. In addition, there were alterations in B cell differentiation with partial blocks in B cell development in the bone marrow. In our current studies, we have focused on their defect in antibody production. When challenged with either NP-CGG (T-dependent antigen) or NP-LPS (T-independent antigens), reduced IgG antibody titers to NP antigens were seen in mice with constitutive reductions in mTOR protein levels, despite equivalent levels of total antibody production; high affinity antibody production was also less. The numbers of germinal centers were reduced in the spleens of the mTORC1/2-compromised mice compared to their wild-type littermates. Fewer B cells from the mTORC1/2-compromised mice were able to undergo class switching from IgM to IgG. In addition, germinal center B cells from these mice exhibited reductions in somatic hypermutation rates of their immunoglobulin loci. Studies are currently underway to evaluate the ability of these mice to respond to an in vivo challenge of live bacteria. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 805. doi:10.1158/1538-7445.AM2011-805