Cellular & Molecular Defects in Human B Cell Development

: 01（）9' cop 新的诊断技术和有针对性的治疗。对原代人B细胞缺陷的研究已经导致对B细胞发育的特定阶段的认识。B细胞谱系的定型发生在淋巴细胞生成的早期，在IG重链基因中有选择的基因重排;这些基因重排启动抗原识别过程，这是适应性免疫的标志。B细胞的进一步成熟的特征在于扩增、分化、运输至外周淋巴结中的特定区室、选择适当的抗原受体、产生B细胞记忆以及最终形成粘膜位点群。伴随着B细胞群的扩增，需要缺失自身反应性克隆。所有这些事件都是相互交织的，但这些相互作用的性质还没有完全理解。本计划项目资助的总体假设是，选定的遗传、细胞和微环境影响对正常B细胞发育至关重要，这些过程中的任何缺陷都可能导致免疫缺陷。本计划项目选择B细胞免疫的四个特定阶段进行研究，项目1：机制 .-. 'C3 _;c. 3楼 -5英寸 �;N (D-� 对明确的人类遗传疾病的研究是阐明正常生理事件的有力工具。这在原发性免疫缺陷疾病中最为明显。特异性免疫缺陷状态的表征已经导致免疫学的显著进步，催化了对这些疾病的更深入理解，并引发了免疫学的发展。 安娜）- �4� CEP 第二章） 项目2：研究B细胞记忆的阻断;项目3：肠粘膜中伊加产生的调节和功能;项目4： B细胞耐受性的一个重要因素。正常保护性免疫的发展对于理解疫苗接种、疾病预防、移植和自身免疫是必不可少的;然而这些免疫反应是如何发展和控制的，需要进一步阐明。在西奈山，我们有一个独特的和宝贵的资源，在我们的主要免疫缺陷计划，这使得仔细研究人类B细胞生物学的选定阶段，本计划项目的主题 Mn3 格兰特. �C�C PHS 398/2590（Rev.11/07） 页面 - 续页格式 `-' .-� ..- ... ）oa` >. ", c=0

: 01()9' cop novel diagnostic techniques and targeted treatments. Studies of primary human B cell defects have led to an appreciation of specific stages of B cell development. Commitment to the B cell lineage occurs early in lymphogenesis with selected gene rearrangements in Ig heavy chain genes; these initiate the process of antigen recognition, a hail mark of adaptive immunity. Further maturation of B cells is characterized by expansion, differentiation, trafficking to specific compartments in peripheral lymph nodes, selection of appropriate antigen receptors, the generation of B cell memory and finally population of mucosal sites. Coupled with the expansion of B cell populations, is the requirement for deletion of self-reactive clones. All of these events are intertwined, but the nature of these interactions are incompletely understood. The overall hypothesis of this Program Project Grant is that selected genetic, cellular and micro-environmental influences are critical to normal B cell development and that defects in any of these processes can result in immune deficiency. This Program Project selects four specific stages of B cell immunity to investigate, Project 1: Mechanisms .-. 'C3 _;c. 3�'o -5" �;N (D-� The study of well defined human genetic disease is a powerful tool in the elucidation of normal physiologic events. This is most evident in the case of the primary immune deficiency diseases. Characterization of specific immune deficiency states has led to remarkable advances in immunology, catalyzing greater understanding of these diseases, and sparking the development of Ana)- �4� cep II) of V(D)J mediated immunodeficiencies; Project 2: Investigating blocks to B cell memory; Project 3: Regulation and function of IgA production in the intestinal mucosa; Project 4: Loss of B cell tolerance in primary immune deficiency. The development of normal protective immunity is essential for understanding vaccination, disease prevention, transplantation, and autoimmunity; yet how these immune responses are developed and controlled, require further elucidation. At Mount Sinai we have a unique and valuable resource in our Primary Immune Deficiency Program; this allows for careful study of selected stages of human B cell biology, the subject of this Program Project MN3 Grant. �-c PHS 398/2590 (Rev. 11/07) Page - Continuation Format Page `-' .-� ..- ... )oa` >.", c=0