%0 Work %T Stat3-Dependent Survival and Stat3-Independent Terminal Differentiation in the B Cell Compartment in IL-6 Transgenic Mice %A Sarah E Staggs %D 2007-12-07 %8 2018-08-30 %R http://localhost/files/tq57nr12c %X IL-6 is a pleiotropic cytokine involved in both immune and non-immune functions. In the immune system, IL-6 induces terminal differentiation of B cells into plasma cells, thereby promoting antibody production. IL-6 stimulates growth of T cells by enhancing the expression of the IL-2 receptor, and IL-6 also causes differentiation of macrophages. IL-6 signaling is dependent upon multiple pathways, most notably the Stat3 signaling pathway. In this study, we examined the role of Stat3 in the functions of IL-6 on B cells using an IL-6 transgenic (Tg) mouse model in which hIL-6 is ubiquitously expressed. We found that IL-6 Tg mice exhibited approximately a 4-fold increase in cell numbers in every mature B cell subset examined, and that this increase in cell numbers is due to enhanced survival rather than an increase in proliferation or an increase in the number of B cell progenitors. Furthermore, the IL-6 Tg mice exhibited approximately a 10- to 20-fold increase in the number of antibody secreting cells. Conditional deletion of Stat3 on the IL-6 Tg background showed a normalization of B cell numbers to wild-type levels in every mature B cell subset examined. However, conditional deletion of Stat3 had no effect on the numbers of antibody secreting cells in the IL-6 Tg mice. These results document a Stat3-independent pathway for IL-6 induced B cell differentiation. %[ 2018-08-30 %9 Dissertation %~ Arch : Northwestern University Institutional Repository %W Northwestern