Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA, 94143, USA.
Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA, 94143, USA.
Curr Opin Immunol. 2018 Dec;55:67-74. doi: 10.1016/j.coi.2018.09.015. Epub 2018 Oct 5.
A substantial fraction of mature naïve B cells recognize endogenous antigens, and this autoreactivity must be controlled to prevent autoantibody secretion. Selective downregulation of the IgM BCR on autoreactive B cells has long been appreciated, and recent findings illustrate how this might impose tolerance. The BCR isotype maintained on autoreactive B cells, IgD, is less sensitive to endogenous antigens than IgM. This reduced sensitivity may be conferred by structural properties of IgD and/or differential association with activating and inhibitory co-receptors. Once activated, autoreactive B cells are normally excluded from rapid plasma cell responses, but they can enter the germinal center and lose their autoreactivity through a mutation-selection process termed clonal redemption.
大量成熟的初始 B 细胞识别内源性抗原，为防止自身抗体分泌，这种自身反应性必须受到控制。长期以来，人们一直认为自身反应性 B 细胞上的 IgM BCR 选择性下调，最近的发现阐明了这如何产生耐受。维持在自身反应性 B 细胞上的 BCR 同种型 IgD 对内源性抗原的敏感性低于 IgM。这种降低的敏感性可能是由 IgD 的结构特性和/或与激活和抑制共受体的不同结合赋予的。自身反应性 B 细胞一旦被激活，通常会被排除在快速浆细胞反应之外，但它们可以进入生发中心，并通过称为克隆救赎的突变选择过程失去自身反应性。
