| First Author | Chen TT | Year | 2016 |
| Journal | J Exp Med | Volume | 213 |
| Issue | 13 | Pages | 3025-3039 |
| PubMed ID | 27849553 | Mgi Jnum | J:237503 |
| Mgi Id | MGI:5812830 | Doi | 10.1084/jem.20151620 |
| Citation | Chen TT, et al. (2016) STAT1 regulates marginal zone B cell differentiation in response to inflammation and infection with blood-borne bacteria. J Exp Med 213(13):3025-3039 |
| abstractText | Marginal zone B (MZ B) cells can rapidly produce antibody in response to infection with blood-borne encapsulated pathogens. Although TLR-mediated activation of MZ B is known to trigger humoral immune response, the signal cascade directing this response remains undefined. Here, we demonstrate that STAT1 plays an essential role in TLR-mediated antibody response of MZ B cells. Further, the TLR-induced IgM response is impaired in a type I and type II IFN-independent manner. Although activation, proliferation, and apoptosis are not affected, both differentiation into plasma cells and IgM production are impaired in Stat1-/- MZ B cells. Interestingly, STAT1 directly regulates the expression of Prdm1 (encodes BLIMP-1) by binding to its promoter, and Prdm1 expression is reduced in Stat1-/- MZ B cells. Restoration of BLIMP-1 to cells rescues TLR-induced IgM response. Moreover, Stat1-/- mice are more susceptible to S. pneumoniae infection, which can be rescued by the serum of bacteria-primed WT mice. The increased susceptibility to S. pneumoniae infection in Stat1-/- mice is also intrinsic to STAT1 requirement in MZ B cells. Collectively, these results define a differential regulation of TLR-mediated activation and differentiation of MZ B cells by STAT1 and reveal a STAT1-dependent, but IFN-independent, antibody response during infection and inflammation. |
