Origins of serum IgA antibodies

血清 IgA 抗体的起源

• 批准号: 9111850
• 负责人: David M Allman
• 金额: $ 40万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9111850
• 关键词: Address; Affect; Antibiotics; Antibodies; Antibody Response; Antigens; Appearance; Automobile Driving; B-Lymphocytes; Bacteria; Bone Marrow; Cell Communication; Cell Differentiation process; Cell Survival; Cells; Cytokine Receptors; Disease; Enteral; Frequencies; Gastrointestinal tract structure; Generations; Germ-Free; Goals; Health; Housing; Immune; Immunity; Immunoglobulin A; Immunoglobulin Genes; Infection; Integrins; Intestines; Kinetics; Knowledge; Lamina Propria; Life; Longevity; Lymphoid Tissue; Microbe; Modeling; Mono-S; Mucosal Immunity; Mucous Membrane; Mus; Plasma Cells; Production; Role; Salmonella typhimurium; Serum; Site; Source; T-Lymphocyte; Testing; Work; commensal microbes; design; enteric pathogen; improved; oral vaccine; pathogen; prevent; research study; response

DESCRIPTION (provided by applicant): Our intent is to define the factors controlling the generation of lasting IgA responses and determine the role of commensal microbes in promoting systemic IgA responses to enteric antigens and pathogens. The central hypothesis underpinning this work is that Segmented Filamentous Bacteria (SFB) promote systemic IgA responses by priming gut-resident T and B cells, thus augmenting the generation of mucosal IgA+-secreting cells that subsequently colonize niches for long-lived plasma cells in the bone marrow. Additional experiments will define the life span of IgA-secreting plasma cells in the gut and the bone marrow, at steady state and in response to an enteric pathogen. Specifically we will: 1) Define the impact of SFB colonization on the bone marrow plasma cell pool, 2) Define the impact of SFB colonization on systemic IgA responses to enteric microbes, 3) Define decay kinetics for IgA+ PCs in the LP and the BM.

描述（由申请人提供）：我们的目的是定义控制持久IgA响应产生的因素，并确定共生微生物在促进全身IgA对肠抗原和病原体的反应中的作用。基于这项工作的主要假设是，分割的丝状细菌（SFB）通过启动肠道居民T和B细胞促进了全身IgA反应，从而增加了粘膜IgA+分泌细胞的产生，从而使骨骨髓中长层状血浆细胞的粘膜菌落的粘膜生成。 其他实验将定义肠道和骨髓中分泌IgA分泌的浆细胞的寿命，并在稳定状态下以及对肠道病原体的响应。 具体而言，我们将：1）定义SFB定殖对骨髓浆细胞池的影响，2）定义SFB定殖对全身IgA对肠性微生物的影响的影响，3）定义LP和BM和BM中IgA+ PC的衰减动力学。