Soraphen A effect on B cells post-stroke

Introduction: Immunomodulatory approaches could advance post-stroke therapy. Previous work demonstrated that Soraphen A (SorA) improves functional recovery, in part, by modulating T cell responses. Here, we demonstrate that SorA also directly or indirectly modulates B cell responses. Methods: Male Nur77GFP mice (12–14 weeks) underwent tMCAO. At reperfusion, mice received intraperitoneal LPS or vehicle; SorA or vehicle was given 2 h later and daily thereafter. B cell activation and differentiation were analyzed by flow cytometry in lungs, spleen, blood, and lymph nodes at 16 h, 2, 3, and 7 d, with GFP indicating antigen-specific activation. Results: While both SorA and lipopolysaccharide (LPS) replenished splenic B cell numbers depleted by stroke, their effects on B cell subsets diverge. SorA also reversed LPS-induced reductions in lung B cell counts and decreased plasma cell counts. Both treatments increased B cell activation and modulated MHC-II expression. In contrast to T cells, the mode of B cell activation was not affected by SorA treatment. Effects of LPS and SorA on B cell populations were most distinct in the lungs. Discussion: These findings demonstrate that the beneficial effects of SorA after stroke are not solely mediated by T cell modulation. Further investigation into SorA’s organ-specific impact on different B cell subtypes is crucial to fully elucidate its mechanisms of action.引言：免疫调节策略可推动卒中后治疗的发展。既往研究表明，索拉芬A（Soraphen A，SorA）可部分通过调节T细胞（T cell）应答改善功能恢复。本研究证实，SorA还可直接或间接调节B细胞（B cell）应答。 方法：选取12~14周龄的雄性Nur77GFP小鼠，构建暂时性大脑中动脉闭塞（tMCAO）模型。再灌注时，小鼠接受腹腔内注射脂多糖（lipopolysaccharide，LPS）或溶媒对照处理；2小时后给予SorA或溶媒对照，此后每日给药一次。分别于造模后16小时、2天、3天及7天，通过流式细胞术分析肺、脾、血液及淋巴结中的B细胞活化与分化情况，其中GFP可指示抗原特异性活化。 结果：尽管SorA与脂多糖（LPS）均能补充卒中诱导耗竭的脾脏B细胞数量，但二者对B细胞亚群的作用存在差异。SorA还可逆转LPS诱导的肺脏B细胞计数降低，并减少浆细胞数量。两种处理均能提升B细胞活化水平并调节主要组织相容性复合体II类（MHC-II）的表达。与T细胞不同，SorA处理不会影响B细胞的活化方式。LPS与SorA对B细胞群体的影响在肺脏中最为显著。 讨论：本研究结果表明，卒中后SorA的获益作用并非仅通过调节T细胞介导。进一步探究SorA对不同B细胞亚群的器官特异性影响，对于全面阐明其作用机制至关重要。