Matsuda Yoshiko, Hiramitsu Takahisa, Li Xiao-Kang, Watanabe Takeshi
Division of Transplant Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Pathogens. 2020 Dec 23;10(1):4. doi: 10.3390/pathogens10010004.
Antibody-mediated allograft rejection (AMR) hinders patient prognosis after organ transplantation. Current studies concerning AMR have mainly focused on the diagnostic value of immunoglobulin G (IgG)-type donor-specific antihuman leukocyte antigen antibodies (DSAs), primarily because of their antigen specificity, whereas the clinical significance of immunoglobulin M (IgM)-type DSAs has not been thoroughly investigated in the context of organ transplantation because of their nonspecificity against antigens. Although consensus regarding the clinical significance and role of IgM antibodies is not clear, as discussed in this review, recent findings strongly suggest that they also have a huge potential in novel diagnostic as well as therapeutic application for the prevention of AMR. Most serum IgM antibodies are known to comprise natural antibodies with low affinity toward antigens, and this is derived from B-1 cells (innate B cells). However, some of the serum IgM-type antibodies reportedly also produced by B-2 cells (conventional B cells). The latter are known to have a high affinity for donor-specific antigens. In this review, we initially discuss how IgM-type antibodies of different origins participate in the pathology of various diseases, directly or through cell surface receptors, complement activation, or cytokine production. Then, we discuss the clinical applicability of B-1 and B-2 cell-derived IgM-type antibodies for controlling AMR with reference to the involvement of IgM antibodies in various pathological conditions.
抗体介导的同种异体移植排斥反应（AMR）会阻碍器官移植后患者的预后。目前关于AMR的研究主要集中在免疫球蛋白G（IgG）型供体特异性抗人白细胞抗原抗体（DSA）的诊断价值上，主要是因为它们具有抗原特异性，而免疫球蛋白M（IgM）型DSA在器官移植背景下的临床意义尚未因其对抗原的非特异性而得到充分研究。尽管关于IgM抗体的临床意义和作用尚未达成共识，但如本综述中所讨论的，最近的研究结果强烈表明，它们在预防AMR的新型诊断和治疗应用中也具有巨大潜力。大多数血清IgM抗体已知是由对抗原亲和力低的天然抗体组成，这些抗体源自B-1细胞（先天性B细胞）。然而，据报道，一些血清IgM型抗体也由B-2细胞（传统B细胞）产生。已知后者对供体特异性抗原有高亲和力。在本综述中，我们首先讨论不同来源的IgM型抗体如何直接或通过细胞表面受体、补体激活或细胞因子产生参与各种疾病的病理过程。然后，我们参照IgM抗体在各种病理状况中的参与情况，讨论B-1和B-2细胞衍生的IgM型抗体在控制AMR方面的临床适用性。
