Pivotal role of STAT3 signaling in germinal center B cell and T follicular helper cell differentiation (IRC3P.458)

Abstract

Abstract Germinal center (GC) B cells and T follicular helper (Tfh) cells are critical for long-lived plasma cell differentiation and high-affinity antibody production in response to T cell-dependent antigens. Previous studies demonstrated that GC formation was intact in the absence of STAT3 in B cells at day 12. However, emerging evidence suggests that IL-21/STAT3 signaling is a potent regulator for B cell differentiation. To better understand the role of STAT3 in the kinetics of GC formation and GC B cell response, we assessed GC B cells at consecutive time points following immunization with antigen OVA. In B cell conditional STAT3-dificient mice, fewer GC and GC B cells were generated upon immunization in the late phase (day 21) but not on day 14 compared with that of control mice. Increased cell death and decreased cell proliferation were found in the STAT3 deficient GC B cells. Consequently, plasma cell differentiation and antibody production were impaired in B cell STAT3-deficient mice. In addition, the Tfh cell response was correlated with the magnitude of the GC B cell response and significantly decreased in B cell STAT3-deficient mice. Furthermore, GC B cells and autoantibody production were also significantly decreased in autoreactive B cell STAT3-deficient mice after apoptotic cell immunization. These data provide new insights into the GC and Tfh differentiation and the function of STAT3 in humoral immune responses.