Department of Internal Medicine, Division of Rheumatology, University of Michigan Medical School, Ann Arbor, Michigan 48109-2200, United States of America.
Mol Med. 2012 Feb 10;18(1):123-37. doi: 10.2119/molmed.2011.00333.
Suppression of the immune system after the resolution of infection or inflammation is an important process that limits immune-mediated pathogenesis and autoimmunity. Several mechanisms of immune suppression have received a great deal of attention in the past three decades. These include mechanisms related to suppressive cytokines, interleukin (IL)-10 and transforming growth factor (TGF)-β, produced by regulatory cells, and mechanisms related to apoptosis mediated by death ligands, Fas ligand (FasL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), expressed by killer or cytotoxic cells. Despite many lines of evidence supporting an important role for B lymphocytes as both regulatory and killer cells in many inflammatory settings, relatively little attention has been given to understanding the biology of these cells, their relative importance or their usefulness as therapeutic targets. This review is intended to give an overview of the major mechanisms of immunosuppression used by B lymphocytes during both normal and inflammatory contexts. The more recent discoveries of expression of granzyme B, programmed death 1 ligand 2 (PD-L2) and regulatory antibody production by B cells as well as the interactions of regulatory and killer B cells with regulatory T cells, natural killer T (NKT) cells and other cell populations are discussed. In addition, new evidence on the basis of independent characterizations of regulatory and killer CD5(+) B cells point toward the concept of a multipotent suppressor B cell with seemingly high therapeutic potential.
抑制免疫系统在感染或炎症得到解决后是一个重要的过程，它限制了免疫介导的发病机制和自身免疫。在过去的三十年中，有几种免疫抑制机制受到了广泛关注。这些机制包括与抑制性细胞因子有关的机制，如调节细胞产生的白细胞介素 (IL)-10 和转化生长因子 (TGF)-β，以及与凋亡有关的机制，凋亡由杀伤细胞或细胞毒性细胞表达的死亡配体 Fas 配体 (FasL) 和肿瘤坏死因子相关凋亡诱导配体 (TRAIL) 介导。尽管有许多证据表明 B 淋巴细胞在许多炎症环境中既是调节细胞又是杀伤细胞，但对这些细胞的生物学、它们的相对重要性或它们作为治疗靶点的有用性的理解相对较少。这篇综述旨在概述 B 淋巴细胞在正常和炎症情况下用于免疫抑制的主要机制。本文还讨论了 B 细胞表达颗粒酶 B、程序性死亡受体 1 配体 2 (PD-L2) 和调节性抗体产生的较新发现，以及调节性和杀伤性 B 细胞与调节性 T 细胞、自然杀伤 T (NKT) 细胞和其他细胞群之间的相互作用。此外，基于对调节性和杀伤性 CD5(+)B 细胞的独立特征的新证据表明，具有潜在高治疗潜力的多能抑制性 B 细胞的概念。
