邊緣區B細胞為單核球增多性李斯特菌感受性之主要介白素10來源

Abstract

後天免疫系統缺乏之 Rag-1 剔除小鼠對於單核球增生性李斯特菌感染具有極高 之耐受性。為了進一步暸解淋巴球在此一特殊現象中扮演的角色，本文利用缺少單一淋巴球系之基因剔除小鼠研究此一現象。相對於缺乏 T 淋巴球系之小鼠，缺乏 B 淋巴球之小鼠感染李斯特菌後呈現較低的細菌數與較高的存活率。其趨勢與Rag-1 剔除小鼠相似。接受邊緣區 B 細胞移植之 Rag-1 剔除小鼠與第十型介白素剔除小鼠具有較高之第十型介白素以及李斯特菌數， 並且γ-干擾素呈現下降的現象；反之接受濾泡性 B 細胞移植之小鼠則無上述現像。另外，第十型介白素抗體能夠中和此一邊緣區 B 細胞依賴型之現象。本文亦利用邊緣區 B 細胞缺乏之B 細胞專一型 Rbpj 剔除小鼠，研究邊緣區 B 細胞對李斯特菌感染所造成之影響。李斯特菌感染之邊緣區 B 細胞缺乏之基因剔除小鼠，呈現與 B 細胞缺乏之小鼠相似之現象，包含較低的李斯特菌數以及更高的存活率。有鑒於已知許多型細胞能夠產生第十型介白素，本文在此更進一步指出邊緣區 B 細胞才是李斯特菌感染時主要產生第十型介白素之細胞，並且造成宿主對於李斯特菌之感受性上升。一般認為，邊緣區 B 細胞在感染疾病中是扮演保護者之角色﹔邊緣區 B 細胞提高宿主對李斯特菌感受性之現象反而與此一觀念大相庭逕。本文提出強力證據，證明邊緣區 B 細胞在李斯特菌感染中扮演不利宿主的角色，此一現象很可能亦發生於其他類型之感染疾病。邊緣區 B 細胞對於其他類型之感染症所扮演之角色，則尚須進一步之研究。

Rag-1-KO mice are highly resistant to Listeria monocytogenes infection. The role played by the many Rag-1-dependent lymphocyte lineages was studied using a genetic approach in which each Rag-1-dependent lymphocyte lineage was eliminated one at a time. Only B cell-deficient Igh-KO mice displayed reduced bacterial load and improved survival upon Listeria infection. Listeria infection of Rag-1-KO and Il-10-KO hosts that had been adoptively transferred with marginal zone B cells, but not follicular B cells, resulted in heightened bacterial load which was accompanied by increased Il-10 and reduced Ifn-γ production. This marginal zone B cell-dependent increase in bacterial load was eliminated by anti-Il-10 mAb. In addition, Listeria infection of marginal zone B cell-deficient Rbpj-cKO mice showed decreased bacterial load and increased survival. Whereas multiple cell types have been shown to be capable of Il-10 production, our results show that the marginal B cell is the most dominant and relevant Il-10 source in the context of Listeria susceptibility. In marked contrast to the generally protective nature of marginal zone B cells in defending against pathogenic infection, our results demonstrate a detrimental role they play in Listeria infection and possibly other infections also.