The Role of IL-10 Secreting MZ B cells in Response to a Bacterial Challenge

分泌 IL-10 的 MZ B 细胞在应对细菌挑战中的作用

• 批准号: 7783778
• 负责人: NICHOLAS W. KIN
• 金额: $ 4.63万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-16 至 2011-01-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7783778
• 关键词: Affect; Antibody Formation; Antigen-Presenting Cells; Antigens; Architecture; Autoimmune Diseases; Autoimmunity; B-Lymphocyte Subsets; B-Lymphocytes; Bacteria; Bacterial Infections; Bion; Blast Cell; Blood; Cells; Data; Development; Enzyme-Linked Immunosorbent Assay; Fluorescence; Genes; Goals; Heating; Immune response; Immune system; Immunization; Immunoglobulin Idiotypes; In Vitro; Interleukin-10; Interleukin-4; Invaded; Location; MAP Kinase Gene; Measures; Messenger RNA; Molecular; Mus; Pharmaceutical Preparations; Plasma; Play; Population; Process; Production; Public Health; Regulation; Reporter; Role; Signal Transduction; Sorting - Cell Movement; Spleen; Staining method; Stains; Streptococcus pneumoniae; Surface; Techniques; Testing; Therapeutic Intervention; Time; Up-Regulation; Western Blotting; Work; anti-IgM; base; cell type; combat; design; fighting; inhibitor/antagonist; interest; killings; mouse model; receptor; response; tool; vaccination strategy

DESCRIPTION (provided by applicant): The overall goal of this proposal is to further our understanding of the development and function of splenic B cells. The splenic B cell population can be divided into the marginal zone (MZ) and follicular (FO) B cell subsets based on anatomical location, cellular surface molecules, and functional immune responses. We are particularly interested in the development of the MZ B cell population, the role it plays in antibody responses, and the receptors that positively or negatively regulate cellular activity. A large expansion of MZ B cells occurs in nearly all established mouse models of autoimmune disease before any signs of pathological autoimmunity are observed. The significance of this phenomenon and its role in the autoimmune disease process has, surprisingly, been poorly investigated. Additionally, the mechanisms governing the activation and regulation of the MZ B cells following a bacterial challenge are not fully understood. Using a variety of cellular and molecular techniques, we propose to test the hypothesis that MZ B cells play an immunoregulatory role via IL-10 secretion in response to a blood-borne bacterial challenge. The findings will provide a better understanding of the mechanism by which MZ B cells respond during a bacterial infection and identify potential targets for therapeutic intervention. The following specific aims are designed to test our hypothesis: Aim 1: Determine if MZ B cells secrete IL-10 in response to a blood-borne bacterial challenge. Working Hypothesis: Antigen-specific MZ B cells secrete IL-10 in response to S. pneumoniae challenge. Aim 2: Determine the role of MZ B cell IL-10 production during response to a blood-borne bacterial challenge. Working Hypothesis: Antigen-specific MZ B cells play an immunoregulatory role via IL-10 secretion following S. pneumoniae challenge. Aim 3: Determine the mechanism by which B cells are activated to secrete IL-10. Working Hypothesis: B cells secrete IL-10 following gram+ and gram- bacterial challenge. RELAVANCE TO PUBLIC HEALTH: The goal of this project is to understand how the immune system fights off invading bacteria and affords protection from becoming sick. Once we understand how the immune system works, we will be able to develop new drugs and vaccination strategies to combat bacterial infections.

描述(申请人提供)：本方案的总体目标是加深我们对脾B细胞的发育和功能的了解。脾B细胞群可根据解剖位置、细胞表面分子和功能免疫反应分为边缘带(MZ)和滤泡(FO)B细胞亚群。我们特别感兴趣的是MZ B细胞群体的发展，它在抗体反应中所起的作用，以及积极或消极地调节细胞活动的受体。在观察到病理性自身免疫的任何迹象之前，几乎所有已建立的自身免疫性疾病的小鼠模型中都会出现MZ B细胞的大量增殖。令人惊讶的是，这种现象的意义及其在自身免疫性疾病过程中的作用一直没有得到很好的研究。此外，细菌攻击后MZ B细胞的激活和调节机制尚不完全清楚。使用各种细胞和分子技术，我们建议检验假设，即MZ B细胞通过分泌IL-10来响应血液传播的细菌挑战而发挥免疫调节作用。这些发现将提供对细菌感染期间MZ B细胞反应机制的更好理解，并确定潜在的治疗干预目标。以下特定目标旨在验证我们的假设：目标1：确定MZ B细胞是否分泌IL-10以响应血液传播的细菌攻击。工作假设：抗原特异的MZ B细胞分泌IL-10以应对肺炎链球菌的攻击。目的2：确定MZ B细胞产生IL-10在血源性细菌攻击应答中的作用。工作假设：肺炎链球菌攻击后，抗原特异性的MZ B细胞通过分泌IL-10发挥免疫调节作用。目的3：确定B细胞被激活分泌IL-10的机制。工作假设：在革兰氏阳性和革兰氏阳性细菌攻击后，B细胞分泌IL-10。与公共卫生的关系：这个项目的目标是了解免疫系统如何抵御入侵的细菌，并提供预防疾病的保护。一旦我们了解了免疫系统是如何工作的，我们就能够开发新的药物和疫苗接种策略来对抗细菌感染。