STAT3 signaling is essential for the germinal center maintenance and pathogenesis of lupus (BA4P.122)

Abstract

Abstract Antibody maturation as well as memory B and plasma cell differentiation occurs primarily in the germinal center (GC). Lupus may develop as a result of enhanced GC activity. Many factors involved in GC reaction, including T follicular helper (Tfh) cells, IL-21, IL-6, play critical roles in lupus pathogenesis. These inflammatory cytokines predominantly activate the STAT3 signaling pathway. Here, we demonstrate that STAT3 signaling in B cells is essential for antibody response as well as GC formation and maintenance. Increased cell apoptosis and down-regulated Bcl-xL expression are found in the STAT3 deficient GC B cells. The Tfh cell response is significantly decreased in B cell STAT3-deficient immunized mice. Further, STAT3 deficiency in autoreactive B cells results in decreased autoantibody production upon immunization with apoptotic cells. Results obtained using B cell STAT3 deficient MRL.Fas(lpr) mice suggest that STAT3 signaling contributes to the pathogenesis of lupus by regulation of autoantibody production. Our findings thus provide new insights into the role of B cell STAT3 signaling in the GC maintenance and pathogenesis of lupus.