Ellis Jason S, Braley-Mullen Helen
Department of Surgery, University of Missouri, Columbia, MO 65212, USA.
Department of Molecular Microbiology & Immunology, University of Missouri, Columbia, MO 65212, USA.
J Clin Med. 2017 Jan 26;6(2):13. doi: 10.3390/jcm6020013.
Experiments with B cell-deficient (B-/-) mice indicate that a number of autoimmune diseases require B cells in addition to T cells for their development. Using B-/- Non-obese diabetic (NOD) and NOD.H-2h4 mice, we demonstrated that development of spontaneous autoimmune thyroiditis (SAT), Sjogren's syndrome and diabetes do not develop in B-/- mice, whereas all three diseases develop in B cell-positive wild-type (WT) mice. B cells are required early in life, since reconstitution of adult mice with B cells or autoantibodies did not restore their ability to develop disease. B cells function as important antigen presenting cells (APC) to initiate activation of autoreactive CD4+ effector T cells. If B cells are absent or greatly reduced in number, other APC will present the antigen, such that Treg are preferentially activated and effector T cells are not activated. In these situations, B-/- or B cell-depleted mice develop the autoimmune disease when T regulatory cells (Treg) are transiently depleted. This review focuses on how B cells influence Treg activation and function, and briefly considers factors that influence the effectiveness of B cell depletion for treatment of autoimmune diseases.
对B细胞缺陷（B-/-）小鼠进行的实验表明，许多自身免疫性疾病的发展除了需要T细胞外，还需要B细胞。利用B-/-非肥胖糖尿病（NOD）小鼠和NOD.H-2h4小鼠，我们证明了B-/-小鼠不会发生自发性自身免疫性甲状腺炎（SAT）、干燥综合征和糖尿病，而这三种疾病在B细胞阳性的野生型（WT）小鼠中都会发生。B细胞在生命早期是必需的，因为用B细胞或自身抗体重建成年小鼠并不能恢复它们发生疾病的能力。B细胞作为重要的抗原呈递细胞（APC）启动自身反应性CD4+效应T细胞的激活。如果B细胞缺失或数量大幅减少，其他APC将呈递抗原，从而优先激活调节性T细胞（Treg），而效应T细胞不会被激活。在这些情况下，当T调节细胞（Treg）被短暂清除时，B-/-或B细胞耗竭的小鼠会发生自身免疫性疾病。本综述重点关注B细胞如何影响Treg的激活和功能，并简要考虑影响B细胞耗竭治疗自身免疫性疾病有效性的因素。
