Grimaldi Christine M, Hicks Ruthmarie, Diamond Betty
Department of Medicine, Columbia University, New York, NY 10032, USA.
J Immunol. 2005 Feb 15;174(4):1775-81. doi: 10.4049/jimmunol.174.4.1775.
Autoreactive B cells arise routinely as part of the naive B cell repertoire. The immune system employs several mechanisms in an attempt to silence these autoreactive cells before they achieve immunocompetence. The BCR plays a central role in B cell development, activation, survival, and apoptosis, and thus is a critical component of the regulation of both protective and autoreactive B cells. The strength of signal mediated by the BCR is determined by numerous factors, both B cell intrinsic and B cell extrinsic. Perturbations in the molecules that regulate the BCR signal strength or that activate pathways that engage in cross talk with the BCR-mediated signaling pathways can lead to the aberrant survival and activation of autoreactive B cells. In this review, we will discuss the some newly identified genetic loci and factors that modulate the BCR signal transduction pathway and, therefore, the regulation of autoreactive B cells. We will also provide evidence for a model of autoreactivity in which a reduction in the strength of the BCR signal allows the survival and the modulation of a naive B cell repertoire replete with autoreactivity.
自身反应性B细胞作为初始B细胞库的一部分经常出现。免疫系统采用多种机制，试图在这些自身反应性细胞获得免疫能力之前使其失活。BCR在B细胞的发育、激活、存活和凋亡中起核心作用，因此是调节保护性B细胞和自身反应性B细胞的关键组成部分。BCR介导的信号强度由众多因素决定，包括B细胞内在因素和B细胞外在因素。调节BCR信号强度的分子或激活与BCR介导的信号通路相互作用的通路的分子发生扰动，可导致自身反应性B细胞异常存活和激活。在本综述中，我们将讨论一些新发现的调节BCR信号转导通路从而调节自身反应性B细胞的基因位点和因子。我们还将为一种自身反应性模型提供证据，在该模型中，BCR信号强度的降低允许富含自身反应性的初始B细胞库存活和调节。
