B Cells: New Insights into Normal versus Dysregulated Function

描述（由申请人提供）：本提案请求支持由大卫J. Rawlings、Frances E.作者声明：隆德Tangye和John G.门罗，将于2011年4月12日至17日在加拿大不列颠哥伦比亚省惠斯勒举行。B淋巴细胞通过一系列高度协调的过程，包括细胞归巢、抗原识别、抗体分泌、抗原呈递和细胞因子释放，在宿主防御感染中发挥关键作用。为了完成这些无数的功能，B细胞必须通过一系列复杂的初级和次级发育、同源平衡和激活触发的检查点。这些检查点决定了随机和分子定向事件，这取决于局部微环境、细胞-细胞相互作用以及与致病性或非致病性生物体的相互作用。这种发育级联中的早期事件促进了多种B细胞抗原受体库的产生，这些受体库对于存活和进入下游效应物群体都是必不可少的。同时，在多个步骤中测试该库的自身反应性，导致特定克隆的丢失或扩增。这些复杂过程的失调可导致免疫缺陷、自身免疫或恶性疾病。2011年Keystone研讨会B细胞会议的总体目标是突出最近对正常与异常B细胞发育和功能的研究，尽可能强调人类研究的数据。 公共卫生相关性：B淋巴细胞或B细胞通过协调先天性和适应性免疫应答在控制细菌、病毒和寄生虫病原体中起关键作用。B细胞功能失调可导致免疫缺陷、自身免疫或恶性疾病。关于B细胞的Keystone研讨会会议将聚集来自参与研究B淋巴细胞生物学的多个学科的研究人员，以分享数据，讨论研究挑战，并进行合作，以便深入了解如何利用这些信息在多种重要的人类疾病中获得治疗益处。

DESCRIPTION (provided by applicant): This proposal requests support for a Keystone Symposia meeting entitled B Cells: New Insights into Normal versus Dysregulated Function, organized by David J. Rawlings, Frances E. Lund, Stuart G. Tangye and John G. Monroe, which will be held in Whistler, British Columbia, Canada from April 12 - 17, 2011. B lymphocytes play crucial roles in host defense against infection via a series of highly coordinated processes that include cell homing, antigen recognition, antibody secretion, antigen presentation, and cytokine release. To accomplish these myriad functions, B cells must maneuver through a complex series of primary and secondary developmental, homoeostatic, and activation-triggered checkpoints. These checkpoints dictate stochastic and molecularly directed events dependent upon local micro-environments, cell-cell interactions, and interactions with pathogenic or non-pathogenic organisms. Early events in this developmental cascade promote the generation of a diverse B cell antigen receptor repertoire that is essential for both survival and entry into downstream effector populations. In parallel, this repertoire is tested for self-reactivity at multiple steps leading to either loss or expansion of specific clones. Dysregulation of these complex processes can lead, alternatively, to immunodeficiency, autoimmunity, or malignant disease. The overall goal of the 2011 Keystone Symposia meeting on B Cells is to highlight recent studies of normal versus abnormal B cell development and function with an emphasis, whenever possible, to data from studies of humans. PUBLIC HEALTH RELEVANCE: B lymphocytes, or B cells, play a critical role in controlling bacterial, viral, and parasitic pathogens via orchestration of both innate and adaptive immune responses. Dysregulated B cell function can lead to immunodeficiency, autoimmunity, or malignant disease. The Keystone Symposia meeting on B Cells will gather investigators from multiple disciplines involved in studying B lymphocyte biology to share data, discuss research challenges, and collaborate in order to provide insight into how to utilize this information for therapeutic benefit in multiple important human disorders.