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Melissa Marie Walker, Bergren W Crute, Andrew Getahun, John C Cambier, B cell Intrinsic and Extrinsic Function of STING in the Antibody Response, The Journal of Immunology, Volume 198, Issue Supplement_1, May 2017, Page 199.15, https://doi.org/10.4049/jimmunol.198.Supp.199.15
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Abstract
Generation of protective immune responses requires coordinate stimulation of innate and adaptive immune systems. An important mediator of innate immunity is STimulator of INterferon Genes (STING), a ubiquitously expressed adaptor molecule that functions in the relay of signals initiated by sensing of cytosolic DNA and bacterial ci-di-nucleotides. Allelic variants of STING, HAQ-STING and R232H-STING, found in 15–20% of humans appear, based on in vitro studies, to be defective in signal relay, suggesting that carriers may be predisposed to certain infections. Our laboratory is engaged in studying the functions of STING, HAQ-STING and R232H-STING.
Here we show that STING promotion of in vivo IgG1 and IgA antibody responses requires both systemic and B cell expression of STING. Analyses of the possible direct effects ci-di-GMP on B cells revealed that CDNs stimulate upregulation of activation markers (CD69 and CD86) as well as apoptotic death, and these responses are dependent on STING expression. Coordinate BCR signals synergize in induction of B cell activation but partially spare cells from apoptosis.
Consistent with defective function of HAQ-STING, B cells from a newly-produced human HAQ and R231H knockin mouse were defective in mounting responses to ci-di-GMP.
Taken together, these data indicate that STING and BCR function coordinately in B cells to promote cell activation and antibody responses. Human carriers of HAQ and R231H STING may be defective in responses to certain immunogens.
