Understanding autoimmunity: Why do B cells sometimes attack our tissues instead of protecting us from infections?

B细胞是一种白色血细胞，是人体免疫系统的一部分，可以产生抗体，保护我们免受感染。在极少数情况下，B细胞产生抗体，攻击组织，导致自身免疫性疾病。查加斯病是由克氏锥虫寄生虫引起的一种被忽视的热带疾病，是全世界传染性心脏病的主要原因，也是西半球影响最大的寄生虫病。作为对T.感染克氏病毒后，免疫系统产生两种抗体：1）对抗寄生虫（保护性），2）对抗心脏（有害）。这是如何发生的，人们知之甚少。该项目的目标是发现T.为此，我们已经产生了新的B细胞四聚体，使我们能够分离和研究寄生虫和心脏特异性B细胞的分子和功能特征。我们还可以获得以下独特的组合：最先进的设施和多组学技术生物发光报告T的新型小鼠模型。克氏锥虫病患者样本库我们将联合收割机B细胞四聚体与流式细胞术、单细胞RNA测序、空间转录组学、RNA显微镜、尖端显微镜和重组抗体相结合，以描绘小鼠和人类寄生虫和心脏特异性B细胞的分子特征、动力学、组织分布和功能。在动物模型和人类样本中进行这项研究将大大增加其转化价值。尽管全球帕金森病或狼疮患者的人数超过了估计数，但恰加斯病几乎没有受到政府的关注。没有疫苗可用，药物治疗有限且有毒。这项研究将产生基础知识，帮助我们开发新的治疗方法，不仅改善这种被忽视的热带疾病患者的生活质量，而且改善一般自身免疫性疾病患者的生活质量。

B cells are white blood cells part of the body's immune system that produce antibodies and protect us from infections. On rare occasions, B cells produce antibodies that attack tissues leading to autoimmune diseases. Chagas disease, a neglected tropical disease caused by Trypanosoma cruzi parasites, is the leading cause of infectious heart disease worldwide and the highest-impact parasitic disease in the Western Hemisphere. In response to T. cruzi infection, the immune system produces two kinds of antibodies: 1) against the parasite (protective), 2) against the heart (harmful). How this happens is poorly understood. The goal of this Project is to discover the signals that drive the immune system to target the heart during T. cruzi infectionFor this, we have generated novel B-cell tetramers that allow us to isolate and study the molecular and functional characteristics of parasite- and heart-specific B cells. We also have access to a unique combination of:State-of-the-art facilities and multi-omics technologiesNovel mouse models of bioluminescent-reporter T. cruzi infectionsA bank of Chagas disease patient samplesWe will combine B-cell tetramers with flow cytometry, single-cell RNA sequencing, spatial transcriptomics, RNAscope, cutting-edge microscopy and recombinant antibodies to delineate molecular signatures, kinetics, tissue distribution and function of parasite- and heart-specific B cells in mice and humans. Running this study in both animal models and human samples will highly increase its translational value.Despite affecting more than the estimated number of people suffering from Parkinson's disease or lupus globally, Chagas disease receives little attention from governments. No vaccines are available and drug treatments are limited and toxic. This research will generate foundational knowledge that will help us produce novel treatments to improve life quality not only of people suffering this neglected tropical disease, but also autoimmune diseases in general.