2011-01-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/654968摘要：第一及第二型干擾素是調控先天及適應性免疫重要的激素，這兩型的干擾素都會活化STAT1，然而，STAT1對B細胞的分化及抗體反應影響則不是十分清楚。我們用STAT1KO的小鼠做實驗結果顯示STAT1可以調控TD和TI抗原所引發的抗體反應。當STAT1KO的小鼠在受到TD抗原的刺激後產生的專一抗體包括IgM及各種IgG包括IgG1, IgG2b, IgG2c及IgG3的量都遠比正常鼠來得低，這種抗體反應的缺陷是起因於T及B細胞本身缺少STAT1的關係，因為當我們把STAT1KO的B細胞送入沒有B細胞的IgHKO或沒有T細胞的TCRKO小鼠身上後，再用抗原去免疫這種嵌合體小鼠，同樣的免疫缺陷也出現。此外，雖然STAT1KO的小鼠經過刺激後發生中心的數目只有些許減少，親和力的熟成及免疫重喚能力在這種小鼠也都有明顯的缺少。此外，在二次抗體反應中抗體分泌細胞數也是比正常小鼠來得少。為了研究在STAT1KO小鼠身上看到的現象是否與第一型干擾素反應失調有關，我們利用另一隻第一型干擾素有缺陷的STAT2次形態突變鼠去做同樣的刺激。結果，STAT1KO小鼠所產生的IgM仍然比STAT2次形態突變鼠來得少。因此，我們認為STAT1KO小鼠表現出來的抗體反應的缺陷是和第一型干擾素的反應失調無關。另外，我們也發現我們TLR刺激活化MZB產生IgM及細胞複製能力也有降低。 總結這些結果， STAT1 可以不用第一型干擾素的方式去正向調控抗體的分型反應及MZB產生IgM的過程。<br> Abstract: STAT1, an important signal mediator of type I and II IFNs, is a critical modulator of innate and adaptive immunity. However, the role of STAT1 in antibody response remains elusive. Using mice lacking STAT1, we have shown that T-dependent (TD) and T-independent (TI) antigen-specific antibodies, including IgG1, IgG2b, IgG2c and IgG3 were decreased as compared to WT mice after immunization in vivo. A similar phenotype was observed in IgHKO and TCRKO mice adoptively transferred with mature B and T cells, respectively, of STAT1KO mice, suggesting that the impaired class switching is intrinsic to the loss of STAT1. Formation of germinal center was, however, only slightly decreased in STAT1KO mice. Affinity maturation and recall response were also impaired in STAT1KO mice. In addition, frequency of ASC was also reduced in the recall response. To investigate the involvement of type I IFNs in impaired antibody response in STAT1KO mice, a STAT2-hypomorphic mouse that displayed impaired IFN response was examined. When compared to STAT2 mutant mice, STAT1KO mice displayed more severe reduction of IgM, suggesting that there is a type I IFN-independent defect in STAT1KO mice in antibody response. Besides, TLR-mediated activation of MZB was also influenced by STAT1. IgM production and cell proliferation was severely impaired in MZB lacking STAT1 In sum, these results suggest that STAT1 positively regulates class switching of antibodies and IgM production by MZB cells.STAT1抗體反應MZBIgMSTAT1antibody responseMZBIgM