| Summary: | 博士 === 國立臺灣大學 === 免疫學研究所 === 105 === Interferon (IFN), including type I and II IFNs, are pleiotropic cytokines that modulate the innate and adaptive immunity. STAT1 is a shared signaling mediator of type I and II IFNs. However, the role of STAT1 in antibody responses remains elusive. Here, we demonstrate that STAT1 positively regulates IgG responses in a B cell- and T cell-dependent manner in response to both thymus-dependent (TD) and thymus-independent (TI) antigens. Moreover, STAT1 also positively regulates IL-4 and anti-CD40 antibody- or TLR-mediated IgM responses of B cells which is more prominent in marginal zone B (MZ B) than follicular B (FO B) cells. Further, the STAT1-mediated IgM response of MZ B cells upon TLR stimulation is IFN-independent. While 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. The attenuated Prdm1 expression in response to TLR is observed not only in Stat1-/- MZ B cells but also in Stat1-/- splenic B-1a cells. 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 reveal a role of STAT1 in B cell differentiation, and IgM and IgG response to TD and TI antigens.
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