MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses

Ming Zeng, Zeping Hu, Xiaolei Shi, Xiaohong Li, Xiaoming Zhan, Xiao Dong Li, Jianhui Wang, Jin Huk Choi, Kuan Wen Wang, Tiana Purrington, Miao Tang, Maggy Fina, Ralph J. DeBerardinis, Eva Marie Y Moresco, Gabriel Pedersen, Gerald M. McInerney, Gunilla B Karlsson Hedestam, Zhijian J. Chen, Bruce Beutler

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

Multivalent molecules with repetitive structures including bacterial capsular polysaccharides and viral capsids elicit antibody responses through B cell receptor (BCR) crosslinking in the absence of T cell help. We report that immunization with these T cell-independent type 2 (TI-2) antigens causes up-regulation of endogenous retrovirus (ERV) RNAs in antigen-specific mouse B cells. These RNAs are detected via a mitochondrial antiviral signaling protein (MAVS)-dependent RNA sensing pathway or reverse-transcribed and detected via the cGAS-cGAMP-STING pathway, triggering a second, sustained wave of signaling that promotes specific immunoglobulin M production. Deficiency of both MAVS and cGAS, or treatment of MAVS-deficient mice with reverse transcriptase inhibitors, dramatically inhibits TI-2 antibody responses. These findings suggest that ERV and two innate sensing pathways that detect them are integral components of the TI-2 B cell signaling apparatus.

Original languageEnglish (US)
Pages (from-to)1486-1492
Number of pages7
JournalScience
Volume346
Issue number6216
DOIs
StatePublished - Dec 19 2014

ASJC Scopus subject areas

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    Zeng, M., Hu, Z., Shi, X., Li, X., Zhan, X., Li, X. D., Wang, J., Choi, J. H., Wang, K. W., Purrington, T., Tang, M., Fina, M., DeBerardinis, R. J., Moresco, E. M. Y., Pedersen, G., McInerney, G. M., Hedestam, G. B. K., Chen, Z. J., & Beutler, B. (2014). MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses. Science, 346(6216), 1486-1492. https://doi.org/10.1126/science.346.6216.1486