Development of B cell memory in allergic asthma

过敏性哮喘中 B 细胞记忆的发展

• 批准号: 10503760
• 负责人: Yee Ling Wu
• 金额: $ 45.43万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-15 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10503760
• 关键词: Address; Affinity; Agonist; Airway Disease; Allergens; Allergic; Allergic inflammation; Anatomy; Antibodies; Antibody Affinity; Antibody Formation; Antibody Response; Antigens; Archives; B cell repertoire; B-Cell Antigen Receptor; B-Cell Development; B-Lymphocyte Subsets; B-Lymphocytes; Bacterial Infections; Biology; Blood Circulation; CCL20 gene; CCR6 gene; Cell Adhesion Molecules; Cells; Characteristics; Development; Disease Progression; Effector Cell; Exposure to; Extrinsic asthma; Gene Expression Profile; Generations; Genetic Transcription; Goals; Heterogeneity; Homing; Human; IgE; IgG1; Immune response; Immunoglobulin Class Switching; Immunoglobulin G; Immunoglobulin M; Immunoglobulin-Secreting Cells; Immunologic Memory; Infection; Inflammation; Intercept; Lung; Lymphoid Tissue; Mediating; Memory B-Lymphocyte; Microscopy; Mucous Membrane; Mus; Output; Parabiosis; Pathogenicity; Patients; Phenotype; Plasma Cells; Population; Positioning Attribute; Prevalence; Production; Pulmonary Inflammation; Respiratory distress; Seeds; Signal Transduction; Site; Spleen; Structure of germinal center of lymph node; Testing; Tissues; Virus Diseases; anti-CD20; chemokine receptor; chronic inflammatory disease; chronic inflammatory lung disease; constriction; experimental study; immune function; lymphoid organ; lymphoid structures; mouse model; novel therapeutic intervention; response; sensitizing antigen; trafficking; transcriptomics

Project Summary/Abstract Allergic asthma is a chronic inflammatory disease of the lungs without cure. Repetitive allergen exposure in the airway leads to the generation of pathogenic immune memory and the excessive production of allergen specific IgE antibodies that mediate inflammation, airway constriction and respiratory distress in patients with allergic asthma. Memory B cells are a key component of immune memory. The phenotypic and functional heterogeneity of MBCs affords their differential antibody responses as well as impact their trafficking, tissue retention and ability to disseminate systemically. In a mouse model of allergic lung inflammation, we have observed stable lung- localized MBCs and evidence for the generation of pathogenic antibody responses in sensitized lungs. We hypothesize that after local antigen sensitization, the lung acquires immune functions reminiscent of those in secondary lymphoid tissues, capable of maintaining long-lived memory B cells as well as generating new MBCs that can recirculate and disseminate in other tissues to mediate systemic allergic inflammation. In this study, we will 1) probe the development of memory B cells (MBCs) in allergic lungs including in-depth characterization of the critical MBC subset that contributes to allergen specific IgE response, and 2) how these MBCs disseminate systemically. We will also 3) explore strategies to intercept the systemic dissemination of pathogenic MBCs to halt the progression of allergic inflammation. These studies will advance our fundamental understanding of memory B cells as well as help devise new therapeutic strategies for allergic asthma.

项目总结/文摘