The increased activity of regulatory B cells (Breg) is known to be involved in immunosuppression during helminth infection, which is characterized by inducing IL-10-producing Breg cells. However, the current knowledge of B cell subsets differentiation and IL-10-independent immunoregulatory mechanisms of B cells in schistosomiasis is insufficient. BALB/c mice were percutaneously infected with cercariae for investigating the profile of B cell subsets during Schistosoma japonicum infection. B cells isolated from the spleen or peritoneal cavity were analyzed for the regulatory phenotype after stimulation with soluble egg antigens (SEA) in vitro. CD4+ 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+ T cells. Furthermore, the in vivo administration of anti-PD-L1 antibody was conducted to investigate the role of PD-L1 in regulating host immunity during infection. 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-β 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 in vitro 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-β. The splenic B cells from infected mice were able to suppress the function of Th1 and Th2 cells in vitro 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+ T cells were also increased in vivo by blocking PD-L1 after infection, although the hepatic pathology was slightly influenced. Our findings revealed that S. japonicum infection modulates the differentiation of B cell subsets that have the capability to affect the CD4+ T cell response. This study contributes to a better understanding of B cells immune response during schistosomiasis.

中文翻译：

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日本血吸虫感染诱导的B细胞表现出多种调节表型并调节CD4 ⁺ T细胞反应

已知在蠕虫感染期间，调节​​性B细胞（Breg）的活性增加与免疫抑制有关，其特征是诱导产生IL-10的Breg细胞。然而，目前对血吸虫病中B细胞亚群分化和IL-10非依赖性B细胞免疫调节机制的了解不足。BALB / c小鼠经尾经皮感染，以调查日本血吸虫感染期间B细胞亚群的分布情况。在体外用可溶性卵抗原（SEA）刺激后，分析从脾脏或腹膜腔分离的B细胞的调节表型。然后将CD4 + T细胞与经过或不经过抗PD-L1抗体预处理的B细胞共培养，以研究感染小鼠的B细胞在调节CD4 + T细胞方面的作用。此外，为了研究PD-L1在感染过程中调节宿主免疫的作用，进行了体内抗PD-L1抗体的给药。与未感染小鼠相比，感染后第8周和第12周腹膜和脾脏B-1a细胞以及边缘区B（MZB）细胞的百分比降低。在脾脏B细胞中，TGF-β表达在感染后第8周增加，但在感染第12周时下降，而PD-L1表达在感染第8和12周时均升高。另外，体外SEA刺激显着促进了腹膜B细胞中IL-10的表达和脾B细胞中CD5的表达，并且SEA刺激的脾和腹膜B细胞优先表达PD-L1和TGF-β。受感染小鼠的脾脏B细胞能够在体外抑制Th1和Th2细胞的功能，但可以扩展Tfh转录因子Bcl6的表达，而通过共培养前阻断B细胞的PD-L1进一步增强了Tfh转录因子Bcl6的表达。此外，感染后，通过阻断PD-L1，体内CD4 + T细胞中的Th2反应和Bcl6表达也增加了，尽管对肝脏病理的影响很小。我们的发现表明，日本血吸虫感染可调节B细胞亚群的分化，而B细胞亚群具有影响CD4 + T细胞反应的能力。这项研究有助于更好地了解血吸虫病期间B细胞的免疫反应。感染后，通过阻断PD-L1，体内CD4 + T细胞中的Th2反应和Bcl6表达也增加了，尽管对肝脏病理的影响很小。我们的发现表明，日本血吸虫感染可调节B细胞亚群的分化，而B细胞亚群具有影响CD4 + T细胞反应的能力。这项研究有助于更好地了解血吸虫病期间B细胞的免疫反应。感染后，通过阻断PD-L1，体内CD4 + T细胞中的Th2反应和Bcl6表达也增加了，尽管对肝脏病理的影响很小。我们的发现表明，日本血吸虫感染可调节B细胞亚群的分化，而B细胞亚群具有影响CD4 + T细胞反应的能力。这项研究有助于更好地了解血吸虫病期间B细胞的免疫反应。