Clatworthy Menna R
Department of Medicine, University of Cambridge, Cambridge, UK.
Transpl Int. 2014 Feb;27(2):117-28. doi: 10.1111/tri.12160. Epub 2013 Aug 4.
There has been increasing interest in the role played by B cells and their associated antibody in the immune response to an allograft, driven by the need to undertake antibody-incompatible transplantation and evidence suggesting that B cells play a role in acute T-cell-mediated rejection and in acute and chronic antibody-mediated rejection. This review focuses on the molecular events, both activating and inhibitory, which control B-cell activation, and considers how this information might inform therapeutic strategies. Potential targets include the BAFF (B-cell-activating factor belonging to the tumour necrosis factor family) and CD40-CD40L pathways and inhibitory molecules, such as CD22 and FcγRIIB. B cells can also play an immunomodulatory role via interleukin (IL)10 production and may contribute to transplant tolerance. The expansion of allograft-specific IL10-producing B cells may be an additional therapeutic goal. Thus, the treatment paradigm required in transplantation has shifted from that of simple B-cell depletion, to that of a more subtle, differential manipulation of different B-cell subsets.
由于进行抗体不相容移植的需求以及有证据表明B细胞在急性T细胞介导的排斥反应以及急性和慢性抗体介导的排斥反应中发挥作用，人们对B细胞及其相关抗体在同种异体移植免疫反应中所起的作用越来越感兴趣。本综述重点关注控制B细胞活化的分子事件，包括激活和抑制事件，并探讨这些信息如何为治疗策略提供依据。潜在的靶点包括BAFF（肿瘤坏死因子家族的B细胞活化因子）和CD40 - CD40L途径以及抑制分子，如CD22和FcγRIIB。B细胞还可通过产生白细胞介素（IL）10发挥免疫调节作用，并可能有助于移植耐受。同种异体移植特异性产生IL10的B细胞的扩增可能是另一个治疗目标。因此，移植所需的治疗模式已从简单的B细胞清除转变为对不同B细胞亚群进行更精细、有差别的操控。
