Panigrahi Anil K, Goodman Noah G, Eisenberg Robert A, Rickels Michael R, Naji Ali, Luning Prak Eline T
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
J Exp Med. 2008 Dec 22;205(13):2985-94. doi: 10.1084/jem.20082053. Epub 2008 Dec 15.
Continued antibody gene rearrangement, termed receptor editing, is an important mechanism of central B cell tolerance that may be defective in some autoimmune individuals. We describe a quantitative assay for recombining sequence (RS) rearrangement that we use to estimate levels of antibody light chain receptor editing in various B cell populations. RS rearrangement is a recombination of a noncoding gene segment in the kappa antibody light chain locus. RS rearrangement levels are highest in the most highly edited B cells, and are inappropriately low in autoimmune mouse models of systemic lupus erythematosus (SLE) and type 1 diabetes (T1D), including those without overt disease. Low RS rearrangement levels are also observed in human subjects with SLE or T1D.
持续的抗体基因重排,即受体编辑,是中枢B细胞耐受的一种重要机制,在一些自身免疫个体中可能存在缺陷。我们描述了一种用于重组序列(RS)重排的定量测定方法,该方法用于估计各种B细胞群体中抗体轻链受体编辑的水平。RS重排是κ抗体轻链基因座中非编码基因片段的重组。在编辑程度最高的B细胞中,RS重排水平最高,而在系统性红斑狼疮(SLE)和1型糖尿病(T1D)的自身免疫小鼠模型中,包括那些没有明显疾病的模型,RS重排水平却异常低。在患有SLE或T1D的人类受试者中也观察到低RS重排水平。