B淋巴细胞在抗CD45RB抗体诱导的移植免疫耐受中的作用  

Role of B cells in CD45RB antibody-induced transplantation immune tolerance

作　　者：邓春艳[1] 张国超[1] 邓绍平[1] 任莉莉[1] 蒋锦杏[1] 俞丽娜[1] 齐晖[1] 李富荣[1] 

机构地区：[1]暨南大学第二临床医学院/深圳市人民医院干细胞与细胞治疗重点实验室,广东深圳518020

出　　处：《中国病理生理杂志》2016年第3期492-498,共7页Chinese Journal of Pathophysiology

基　　金：国家973前期专项(No.2007CB516811);国家自然科学基金资助项目(No.30772042);深圳市科技计划(No.201001005)

摘　　要：目的:探讨B淋巴细胞在抗CD45RB抗体诱导的移植免疫耐受中的作用。方法:抗CD45RB抗体对BALB/c裸鼠进行预处理后制备脾脏单细胞悬液,与BALB/c小鼠T淋巴细胞和C57BL/6小鼠脾细胞混合培养,流式细胞术分析Th1、Th2、Treg和Tm淋巴细胞。以B6.μMT^(-/-)小鼠为受体、BALB/c小鼠为供体建立皮肤移植模型,移植后向受体鼠腹腔注射抗CD45RB单抗,监测脾淋巴细胞CD3^+CD45RB^(hi)细胞比例。在混合淋巴培养过程中加入抗CD45RB单抗,分离B细胞,建立以BALB/c小鼠为供体、B6.μMT^(-/-)小鼠为受体的心脏移植模型,通过尾静脉注射B细胞给B6.μMT^(-/-)小鼠,观察受体鼠生存期和B细胞分布。结果:在裸鼠体内用抗CD45RB抗体处理过的B淋巴细胞,与T淋巴细胞混合培养时,可使Treg和Th2淋巴细胞比例明显升高,Th1淋巴细胞的比例明显下降,Tm细胞无明显变化。在体内B淋巴细胞缺失的情况下,抗CD45RB抗体依然能够降低T细胞表面CD45RB的表达,与对照组B淋巴细胞存在组相比,抗CD45RB抗体对T淋巴细胞表面CD45RB下调更为快速,但最终CD3^+CD45RB^(hi)T细胞比例无明显变化。体外抗CD45RB抗体处理过的B淋巴细胞可以延长受体鼠的生存时间。B6.μMT^(-/-)鼠在接受抗CD45RB抗体处理的B细胞并进行同种异体心脏移植后,B细胞可向胸腺迁移。结论:在抗CD45RB抗体诱导的免疫耐受中,B淋巴细胞可能通过介导各T淋巴细胞亚群比例发挥着重要作用,且在中枢耐受中也起到一定作用,但是仅靠B淋巴细胞无法形成完全耐受。AIM：To investigate the role of B cells in CD45 RB antibody-induced transplantation immune tolerance.METHODS：Single cell suspension was made from the spleen of BALB/c nude mice disposed by CD45 RB antibody,then mixed cultured with T cells of BALB/c mice and spleen cells of C57 BL/6 mice.The Th1,Th2,Treg and Tm cells were monitored by flow cytometry during the culture process.The skin graft model was set up with B6.μMT^-/-ice as receptors and BALB/c mice as donors.CD45 RB antibody was intraperitoneally injected into the receptors after transplantation and then CD3^＋CD45RB^hi cells were detected by flow cytometry.In another mixed lymphocyte culture,CD45 RB antibody was added,and then B cells were isolated and injected into B6.μMT^-/-ice through the tail vein.The heart transplantation model was established with B6.μMT^-/-ice as receptors and BALB/c mice as donors,and then the survival and the migration of B cells to the thymus were observed.RESULTS：When T lymphocytes were co-cultured with B lymphocytes treated with anti-CD45 RB monoclonal antibody（ m Ab） in vivo,the percentages of Th2 and Treg cells were up-regulated and Th1 cells were down-regulated,but Tm cells were not altered as compared with the control.In vivo without B lymphocytes,anti-CD45 RB m Ab also down-regulated the expression of CD45 RB in T lymphocytes.The reduction was faster and the percentage of CD3^＋CD45RB^hiT cells was not altered as compared with the control.The B lymphocytes treated with anti-CD45 RB m Ab in vitro prolonged the lifetime of receptor in heart transplantation model but failed to induce complete tolerance.After recieving B cells treated with anti-CD45 RB m Ab and allogeneic heart transplantation,B cells migrated to the thymus in B6.μMT^-/-ice.CONCLUSION：B lymphocytes play a definite role in the transplantation immune tolerance induced by anti-CD45 RB m Ab through their affection on T-cell subgroups and also in the central tolerance.However,the induction of immune tolerance can not only rely on B cells.

关 键 词：CD45RB抗体 移植 免疫耐受 

分 类 号：R392.4[医药卫生—免疫学] R363[医药卫生—基础医学]