B-Cell Activation and Tolerance Mediated by B-Cell Receptor, Toll-Like Receptor and Survival Signal Crosstalk in SLE Pathogenesis
Technical Report,15 Aug 2014,14 Aug 2015
University of Pennsylvania Philadelphia United States
Pagination or Media Count:
We previously found that B cell receptor BCR-delivered TLR9 agonists initiate a response involving proliferation followed by abrupt cell death furthermore, responding cells are rescued by survival cytokines. We posited this as a normal immune response-limiting mechanism that, if thwarted, may lead to persistence of self-reactive antibody-secreting cells. With this proposal we seek to characterize the pathways leading to post-proliferative death and rescue, and to determine how different forms of rescue lead to alternative differentiation outcomes. Accordingly, the most significant finding during the first year research period is that in the context of BCR-delivered TLR9 signals, IL-21 promotes and IL-4opposes the T-betCD11c ABC age-associated B cell fate that is associated with humoral autoimmune disease.