Firl Daniel J, Benichou Gilles, Kim James I, Yeh Heidi
Transplant Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Transplant Center, Massachusetts General Hospital, Harvard Medical School , Boston, MA , USA.
Front Immunol. 2017 Feb 2;8:80. doi: 10.3389/fimmu.2017.00080. eCollection 2017.
B lymphocytes contribute to acute and chronic allograft rejection through their production of donor-specific antibodies (DSAs). In addition, B cells present allopeptides bound to self-MHC class II molecules and provide costimulation signals to T cells, which are essential to their activation and differentiation into memory T cells. On the other hand, both in laboratory rodents and patients, the concept of effector T cell regulation by B cells is gaining traction in the field of transplantation. Specifically, clinical trials using anti-CD20 monoclonal antibodies to deplete B cells and reverse DSA had a deleterious effect on rates of acute cellular rejection; a peculiar finding that calls into question a central paradigm in transplantation. Additional work in humans has characterized IL-10-producing B cells (IgM memory and transitional B cells), which suppress the proliferation and inflammatory cytokine productions of effector T cells . Understanding the mechanisms of regulating the alloresponse is critical if we are to achieve operational tolerance across transplantation. This review will focus on recent evidence in murine and human transplantation with respect to non-traditional roles for B cells in determining clinical outcomes.
B淋巴细胞通过产生供体特异性抗体（DSA）参与急性和慢性同种异体移植排斥反应。此外，B细胞呈递与自身MHC II类分子结合的同种异体肽，并向T细胞提供共刺激信号，这对于T细胞的激活以及分化为记忆T细胞至关重要。另一方面，在实验啮齿动物和患者中，B细胞对效应T细胞的调节概念在移植领域越来越受到关注。具体而言，使用抗CD20单克隆抗体清除B细胞并逆转DSA的临床试验对急性细胞排斥率产生了有害影响；这一奇特的发现对移植中的一个核心范式提出了质疑。在人类中的其他研究已经对产生IL-10的B细胞（IgM记忆B细胞和过渡性B细胞）进行了表征，这些细胞可抑制效应T细胞的增殖和炎性细胞因子的产生。如果我们要在移植中实现操作性耐受，那么了解调节同种异体反应的机制至关重要。本综述将重点关注小鼠和人类移植中关于B细胞在决定临床结果方面的非传统作用的最新证据。
