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However, the current knowledge of B cell subsets differentiation and IL-10-independent immunoregulatory mechanisms of B cells in schistosomiasis is insufficient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>BALB\/c mice were percutaneously infected with cercariae for investigating the profile of B cell subsets during<jats:italic>Schistosoma japonicum<\/jats:italic>infection. B cells isolated from the spleen or peritoneal cavity were analyzed for the regulatory phenotype after stimulation with soluble egg antigens (SEA)<jats:italic>in vitro<\/jats:italic>. CD4<jats:sup>+<\/jats:sup>T cells were then cocultured with B cells pretreated with or without anti-PD-L1 antibody for investigating the role of B cells from infected mice on regulating CD4<jats:sup>+<\/jats:sup>T cells. Furthermore, the<jats:italic>in vivo<\/jats:italic>administration of anti-PD-L1 antibody was conducted to investigate the role of PD-L1 in regulating host immunity during infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The percentages of peritoneal and splenic B-1a cells, as well as marginal zone B (MZB) cells were decreased at eight and twelve weeks after infection compared to those from uninfected mice. In splenic B cells, TGF-\u03b2 expression was increased at eight weeks but declined at twelve weeks of infection, and PD-L1 expression was elevated at both eight and twelve weeks of infection. In addition, SEA stimulation<jats:italic>in vitro<\/jats:italic>significantly promoted the expression of IL-10 in peritoneal B cells and CD5 in splenic B cells, and the SEA-stimulated splenic and peritoneal B cells preferentially expressed PD-L1 and TGF-\u03b2. The splenic B cells from infected mice were able to suppress the function of Th1 and Th2 cells<jats:italic>in vitro<\/jats:italic>but to expand the expression of Tfh transcription factor Bcl6, which was further enhanced by blocking PD-L1 of B cells before co-cultivation. Moreover, Th2 response and Bcl6 expression in CD4<jats:sup>+<\/jats:sup>T cells were also increased<jats:italic>in vivo<\/jats:italic>by blocking PD-L1 after infection, although the hepatic pathology was slightly influenced.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings revealed that<jats:italic>S. japonicum<\/jats:italic>infection modulates the differentiation of B cell subsets that have the capability to affect the CD4<jats:sup>+<\/jats:sup>T cell response. This study contributes to a better understanding of B cells immune response during schistosomiasis.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13071-020-04015-3","type":"journal-article","created":{"date-parts":[[2020,4,2]],"date-time":"2020-04-02T14:57:11Z","timestamp":1585839431000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["B cells induced by Schistosoma japonicum infection display diverse regulatory phenotypes and modulate CD4+ T cell response"],"prefix":"10.1186","volume":"13","author":[{"given":"Junli","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjun","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,20]]},"reference":[{"key":"4015_CR1","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/nri843","volume":"2","author":"EJ Pearce","year":"2002","unstructured":"Pearce EJ, MacDonald AS. 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