2012-01-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/656761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。有趣的是，IgM抗體反應的缺陷只有在B細胞嵌合體小鼠身上才看到。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的能力也有降低，但在IFNRKO小鼠的MZB並沒有看到相同的缺陷。 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 remainselusive. Using mice lacking STAT1, we have shown thatT-dependent (TD) and T-independent (TI) antigen-specificantibodies, including IgM and IgG subtypes, IgG1, IgG2b,IgG2c and IgG3, were decreased as compared to WT miceafter immunization in vivo. A similar phenotype wasobserved in IgHKO and TCRKO mice adoptively transferredwith mature B and T cells, respectively, of STAT1KO mice,suggesting that the impaired antibody response is intrinsicto the loss of STAT1. Interestingly, impaired IgM responsewas only observed in B cell chimeric mice. To investigate theinvolvement of type I IFNs in impaired antibody response inSTAT1KO mice, a STAT2-hypomorphic mouse that displayedimpaired IFN response was examined. When compared toSTAT2 mutant mice, STAT1KO mice displayed more severereduction of IgM, suggesting that there is a type IIFN-independent defect of STAT1KO mice in IgM response.Besides, TLR-mediated IgM production was severelyimpaired in marginal zone B-cell (MZB) lacking STAT1.However, the defect was not observed in IFNRKO MZB cells.In sum, these results suggest that STAT1 positivelyregulates class switching of antibodies and IgM productionby MZB cells.STAT1抗體反應MZBIgMSTAT1antibody responseMZBIgM