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（由申请人提供）：该提案的总体目标是进一步了解脾脏B细胞的发展和功能。基于解剖位置，细胞表面分子和功能性免疫反应，可以将脾脏B细胞群体分为边缘区（MZ）和卵泡（FO）B细胞子集。我们对MZ B细胞群的发展，抗体反应中的作用以及对细胞活性的积极或负调节细胞活性的受体特别感兴趣。在观察到任何病理自身免疫迹象之前，几乎所有已建立的自身免疫性疾病的小鼠模型中，MZ B细胞的大量扩张发生。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受到了很少的研究。另外，在细菌挑战后控制MZ B细胞激活和调节的机制尚未完全了解。我们建议使用多种细胞和分子技术，提议检验以下假设：MZ B细胞通过IL-10分泌发挥了免疫调节作用，以应对血液传播的细菌挑战。这些发现将更好地理解MZ B细胞在细菌感染过程中反应的机制，并确定治疗干预的潜在靶标。以下特定目的旨在检验我们的假设：目标1：确定MZ B细胞是否响应血源性细菌挑战而分泌IL-10。工作假设：抗原特异性MZ B细胞分泌IL-10，以应对肺炎链球菌挑战。 AIM 2：确定MZ B细胞IL-10在对血液传播细菌挑战的反应过程中的作用。工作假设：抗原特异性MZ B细胞在肺炎链球菌挑战后通过IL-10分泌起免疫调节作用。 AIM 3：确定激活B细胞分泌IL-10的机制。工作假设：B细胞在革兰氏+和革兰氏菌挑战后分泌IL-10。对公共卫生的兴趣：该项目的目的是了解免疫系统如何与入侵细菌作斗争，并保护免于生病。一旦我们了解了免疫系统的工作原理，我们将能够开发新药和疫苗接种策略来打击细菌感染。