Liu Xiaohe, Wysocki Lawrence J, Manser Tim
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
J Immunol. 2007 Apr 15;178(8):5035-47. doi: 10.4049/jimmunol.178.8.5035.
Levels of AgR (BCR) expression are regulated during B cell development, activation, and induction of tolerance. The mechanisms responsible for and consequences of this regulation are poorly understood. We have described a class of DNA-based autoantigen-reactive B cell that down-regulates BCR expression during development to mature follicular phenotype. In this study, we show that at immature stages of primary differentiation, individual B cells of this type can dynamically modulate levels of expression of BCR in inverse proportion to degree of autoantigen engagement and induced BCR signaling. These adjustments in BCR expression are not associated with cell death, BCR revision, or altered development, and do not require TLR 9. Strikingly, modulation of BCR subunit gene RNA levels and transcription parallels these changes in BCR expression, indicating a direct link between autoantigen-BCR interactions of this type and regulation of transcription of BCR-encoding loci. We propose that this adaptive process allows this class of autoreactive B cell to avoid conventional tolerance pathways and promotes development to mature phenotype.
在B细胞发育、激活和耐受诱导过程中，AgR（BCR）的表达水平受到调控。目前对这种调控的机制及其后果了解甚少。我们已经描述了一类基于DNA的自身抗原反应性B细胞，它们在发育过程中会下调BCR表达，以形成成熟的滤泡表型。在本研究中，我们发现，在初级分化的未成熟阶段，这类B细胞个体能够动态调节BCR的表达水平，且与自身抗原结合程度和诱导的BCR信号呈反比。BCR表达的这些调整与细胞死亡、BCR重排或发育改变无关，也不需要TLR 9。令人惊讶的是，BCR亚基基因RNA水平和转录的调节与BCR表达的这些变化平行，表明这类自身抗原-BCR相互作用与BCR编码基因座转录调控之间存在直接联系。我们提出，这种适应性过程使这类自身反应性B细胞能够避开传统的耐受途径，并促进其向成熟表型发育。
