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B 细胞调节策略在改善移植结局中的作用。

B cell modulation strategies in the improvement of transplantation outcomes.

机构信息

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Mol Immunol. 2020 Sep;125:140-150. doi: 10.1016/j.molimm.2020.06.028. Epub 2020 Jul 15.

Abstract

Successful transplantation outcome is the final goal in most end stage and nonfunctional organs; however, despite using different therapeutic strategies, antibody-mediated rejection is still a big obstacle. B cells have a key role in transplant rejection by several functions, such as antibody production, antigen presenting, contribution in T cell activation, forming the germinal center, and tertiary lymphoid organs. Therefore, B cells modulation seems to be very crucial in transplant outcome. A double-edged sword function is considered for B cells during transplantation; On the one hand, antibody production against the transplanted organ induces antibody-mediated rejection. On the other hand, IL10 production by regulatory B (Breg) cells induces graft tolerance. Nowadays, several monoclonal antibodies (mAb) are available for B cell modulation that are routinely used in transplant recipients, among which rituximab (anti-CD20 mAb) act in eliminating B cells. However, there are some other monoclonal antibodies, such as epratuzumab and Inotuzumab ozogamicin (IO), which exert anti-CD22 activity, resulting in disruption of B cell functions and induction of tolerance in autoimmune disease or B cell malignancies; that notwithstanding, these mAbs have not yet been tried in transplantation. In this review, we focus on different methods for modulating the activity of B cells as well as induction of Breg cells, aiming to prevent the allograft rejection.

摘要

成功的移植结果是大多数终末期和无功能器官的最终目标;然而,尽管采用了不同的治疗策略,抗体介导的排斥反应仍然是一个巨大的障碍。B 细胞通过多种功能在移植排斥中起着关键作用,例如抗体产生、抗原呈递、促进 T 细胞激活、形成生发中心和三级淋巴器官。因此,B 细胞的调节似乎在移植结果中非常重要。在移植过程中,B 细胞被认为具有双重作用;一方面,针对移植器官的抗体产生会导致抗体介导的排斥反应。另一方面,调节性 B(Breg)细胞产生的 IL10 会诱导移植物耐受。如今,有几种用于 B 细胞调节的单克隆抗体(mAb)可用于移植受者,其中利妥昔单抗(抗 CD20 mAb)用于消除 B 细胞。然而,还有其他一些单克隆抗体,如依帕珠单抗和依妥珠单抗奥佐米星(IO),它们具有抗 CD22 活性,导致 B 细胞功能障碍,并在自身免疫性疾病或 B 细胞恶性肿瘤中诱导耐受;尽管如此,这些 mAb 尚未在移植中尝试过。在这篇综述中,我们重点介绍了调节 B 细胞活性和诱导 Breg 细胞的不同方法,旨在防止同种异体移植排斥反应。

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