Yurasov Sergey, Tiller Thomas, Tsuiji Makoto, Velinzon Klara, Pascual Virginia, Wardemann Hedda, Nussenzweig Michel C
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021, USA.
J Exp Med. 2006 Oct 2;203(10):2255-61. doi: 10.1084/jem.20061446. Epub 2006 Sep 11.
A majority of the antibodies expressed by nascent B cells in healthy humans are self-reactive, but most of these antibodies are removed from the repertoire during B cell development. In contrast, untreated systemic lupus erythematosus (SLE) patients fail to remove many of the self-reactive and polyreactive antibodies from the naive repertoire. Here, we report that SLE patients in clinical remission continue to produce elevated numbers of self-reactive and polyreactive antibodies in the mature naive B cell compartment, but the number of B cells expressing these antibodies is lower than in patients with active disease. Our finding that abnormal levels of self-reactive mature naive B cells persist in the majority of patients in clinical remission suggests that early checkpoint abnormalities are an integral feature of SLE.
健康人体内新生B细胞表达的大多数抗体是自身反应性的,但这些抗体中的大多数在B细胞发育过程中从抗体库中被清除。相比之下,未经治疗的系统性红斑狼疮(SLE)患者无法从初始抗体库中清除许多自身反应性和多反应性抗体。在此,我们报告临床缓解期的SLE患者在成熟的初始B细胞区室中继续产生数量升高的自身反应性和多反应性抗体,但表达这些抗体的B细胞数量低于活动性疾病患者。我们发现,大多数临床缓解期患者中持续存在异常水平的自身反应性成熟初始B细胞,这表明早期检查点异常是SLE的一个固有特征。