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STAT1 regulates marginal zone B cell differentiation in response to inflammation and infection with blood-borne bacteria
| Content Provider | Scilit |
|---|---|
| Author | Chen, Ting-Ting Tsai, Ming-Hsun Kung, John T. Lin, Kuo-I Decker, Thomas Lee, Chien-Kuo |
| Copyright Year | 2016 |
| Description | Journal: The Journal of experimental medicine 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. |
| Related Links | https://rupress.org/jem/article-pdf/213/13/3025/853496/jem_20151620.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154933/pdf https://rupress.org/jem/article-pdf/213/13/3025/1163755/jem_20151620.pdf |
| ISSN | 00221295 |
| DOI | 10.1084/jem.20151620 |
| Journal | The Journal of experimental medicine |
| Issue Number | 13 |
| Volume Number | 213 |
| Language | English |
| Publisher | Rockefeller University Press |
| Publisher Date | 2016-11-14 |
| Access Restriction | Open |
| Subject Keyword | Journal: The Journal of experimental medicine Research and Experimental Medicine Differentiation Tlr Mediated Activation |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology |
