TY - JOUR
T1 - MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses
AU - Zeng, Ming
AU - Hu, Zeping
AU - Shi, Xiaolei
AU - Li, Xiaohong
AU - Zhan, Xiaoming
AU - Li, Xiao Dong
AU - Wang, Jianhui
AU - Choi, Jin Huk
AU - Wang, Kuan Wen
AU - Purrington, Tiana
AU - Tang, Miao
AU - Fina, Maggy
AU - DeBerardinis, Ralph J.
AU - Moresco, Eva Marie Y
AU - Pedersen, Gabriel
AU - McInerney, Gerald M.
AU - Hedestam, Gunilla B Karlsson
AU - Chen, Zhijian J.
AU - Beutler, Bruce
PY - 2014/12/19
Y1 - 2014/12/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84919443956&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84919443956&partnerID=8YFLogxK
U2 - 10.1126/science.346.6216.1486
DO - 10.1126/science.346.6216.1486
M3 - Article
C2 - 25525240
AN - SCOPUS:84919443956
SN - 0036-8075
VL - 346
SP - 1486
EP - 1492
JO - Science
JF - Science
IS - 6216
ER -