A B-Cell Gene for Lupus

摘要 最近，几项全基因组关联研究（GWAS）分析 已经在结缔组织疾病如系统性狼疮 红斑和系统性硬化症。有趣的是，多个B细胞基因 包括BANK1、BLK、CSK、PTPN22和IRF8。重要的是， 前四个代表在B细胞信号传导中起关键作用的信号分子， 基本上通过中心轴控制BCR信号强度。这些基因如何 引起系统性自身免疫的功能知之甚少。全身性 自身免疫性疾病在女性中更常见， 二态性的理解很少。我们最近培育出了新的菌株 这可能有助于阐明疾病基因和女性性别对 B细胞活化增强，免疫耐受和自身抗体破坏 在全身性结缔组织疾病中产生。更好地理解 这些疾病的致病机制也将为 更好的治疗方法

ABSTRACT Over the recent past, several genome-wide association study (GWAS) analyses have been conducted in connective tissue diseases such as Systemic lupus erythematosus and Systemic Sclerosis. Interestingly, multiple B-cell genes have been uncovered, including BANK1, BLK, CSK, PTPN22 and IRF8. Importantly, the first four represent signaling molecules that play key roles in B-cell signaling, essentially controlling BCR signal strength via a central axis. How these genes function to cause systemic autoimmunity is poorly understood. Both systemic autoimmune diseases are commoner in females, and the reasons for this dimorphism are poorly understood. We have recently generated novel strains that may help elucidate the contributions of disease genes and female gender to heightened B-cell activation, breach of immune tolerance and autoantibody production in systemic connective tissue diseases. A better understanding of the pathogenic mechanisms underlying these disease will also pave the way towards better therapeutics.