| First Author | Tang CA | Year | 2021 |
| Journal | Cell Mol Immunol | Volume | 18 |
| Issue | 4 | Pages | 1016-1031 |
| PubMed ID | 32999453 | Mgi Jnum | J:343151 |
| Mgi Id | MGI:7564176 | Doi | 10.1038/s41423-020-00552-0 |
| Citation | Tang CA, et al. (2021) STING regulates BCR signaling in normal and malignant B cells. Cell Mol Immunol 18(4):1016-1031 |
| abstractText | STING is an endoplasmic reticulum (ER)-resident protein critical for sensing cytoplasmic DNA and promoting the production of type I interferons; however, the role of STING in B cell receptor (BCR) signaling remains unclear. We generated STING V154M knock-in mice and showed that B cells carrying constitutively activated STING specifically degraded membrane-bound IgM, Igalpha, and Igbeta via SEL1L/HRD1-mediated ER-associated degradation (ERAD). B cells with activated STING were thus less capable of responding to BCR activation by phosphorylating Igalpha and Syk than those without activated STING. When immunized with T-independent antigens, STING V154M mice produced significantly fewer antigen-specific plasma cells and antibodies than immunized wild-type (WT) mice. We further generated B cell-specific STING(KO) mice and showed that STING(KO) B cells indeed responded to activation by transducing stronger BCR signals than their STING-proficient counterparts. When B cell-specific STING(KO) mice were T-independently immunized, they produced significantly more antigen-specific plasma cells and antibodies than immunized STING(WT) mice. Since both human and mouse IGHV-unmutated malignant chronic lymphocytic leukemia (CLL) cells downregulated the expression of STING, we explored whether STING downregulation could contribute to the well-established robust BCR signaling phenotype in malignant CLL cells. We generated a STING-deficient CLL mouse model and showed that STING-deficient CLL cells were indeed more responsive to BCR activation than their STING-proficient counterparts. These results revealed a novel B cell-intrinsic role of STING in negatively regulating BCR signaling in both normal and malignant B cells. |
