Accession Number : AD1024690

Title :   B-Cell Activation and Tolerance Mediated by B-Cell Receptor, Toll-Like Receptor, and Survival Signal Crosstalk in SLE Pathogenesis

Descriptive Note : Technical Report,15 Aug 2015,14 Aug 2016

Corporate Author : Trustees of the University of Pennsylvania Philadelphia United States

Personal Author(s) : Cancro,Michael P ; Scholz,Jean L

Full Text :

Report Date : 01 Sep 2016

Pagination or Media Count : 32

Abstract : 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. In 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. During the first year period we showed that in the context of BCR-delivered TLR9 signals, IL-21 promotes and IL-4 opposes the T-bet CD11c B cell fate. In the current reporting period, we have extended these findings to show that IFN-gamma also promotes the Tbet fate, and that B cells with this phenotype are antigen-experienced cells that emerge in both normal responses to viral infections as well as in autoimmune scenarios. We have forwarded a theoretical framework to explain the link between these activation requisites and humoral autoimmunity.

Descriptors :   medical research , receptors(physiology) , cells(biology) , pathogenesis , autoimmune diseases , cell physiological processes , antiinfective agents , autoimmunity

Subject Categories : Medicine and Medical Research
      Anatomy and Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE