Age-Associated B Cells Specialized for Immunity to Pathogens?

与年龄相关的 B 细胞专门针对病原体具有免疫能力？

• 批准号: 10401919
• 负责人: SUSAN L SWAIN
• 金额: $ 20.94万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10401919
• 关键词: 2019-nCoV; Affect; Age; Aging; Agonist; Antibodies; Antibody Affinity; Antibody Response; Antigens; Autoimmunity; Automobile Driving; B cell differentiation; B-Cell Development; B-Lymphocyte Subsets; B-Lymphocytes; Body Weight decreased; Bronchoalveolar Lavage; CD4 Positive T Lymphocytes; COVID-19; Cell Count; Cell Lineage; Cell physiology; Cells; Dangerousness; Development; Elderly; Ensure; Exposure to; Failure; Future; Generations; Genes; Germ-Free; Goals; Helper-Inducer T-Lymphocyte; Immune; Immune response; Immunity; Immunoglobulin Class Switching; Immunoglobulin-Secreting Cells; Immunotherapy; In Situ; Infection; Inflammatory; Influenza; Influenza A virus; Lead; Learning; Life; Lung; Lymphocyte; Mediating; Memory B-Lymphocyte; Mus; Mutation; Nature; Pathway interactions; Phenotype; Plasma Cells; Population; Recurrence; Role; Serum; Severe Acute Respiratory Syndrome; Signal Transduction; Spanish flu; Spleen; Structure of germinal center of lymph node; Supporting Cell; T-Lymphocyte; TLR7 gene; Vaccination; Vaccine Design; Vaccines; Virus; Virus Diseases; adaptive immune response; aged; antibody transfer; antigen challenge; base; cytokine; improved; influenza infection; influenza virus strain; influenza virus vaccine; mortality; pandemic disease; pathogen; pathogenic virus; programs; response; stem; vaccine strategy

SUMMARY: Age-associated B cells: Specialized for Immunity to Pathogens? With age the generation of T follicular helpers from naive CD4 T cells and germinal center B cells from follicular B cells, that are both needed for the generation of high affinity antibody (Ab), become compromised. Most current vaccines for influenza in the elderly are not effective at inducing these critical responses. Thus, the elderly, though protected by Ab already in place for pathogens encountered earlier in life, are highly susceptible to new strains of virus (e.g. influenza) and newly emerged pathogens (e.g. COVID-19). We noted the generation of an unusual population of antibody-secreting B cells to live influenza infection in aged mice, that we found is derived by stimulation of recently described "age-associated B cells" (ABC). One population of influenza-induced ABC (iABC) are generated independently of CD4 T cell help, but strictly depend on stimulation by pathogen- associated "danger" signals. Recently we found that when help is available, a GCB-like response can instead be induced and produce plasma cells. We also found ABC develop in germ-free mice supporting the intrinsic nature of the age-associated ABC development. Notably, ABC are the predominant naïve B cells that respond in aged mice. Here we will define the signals required from antigen and pathogen-recognition and from CD4 help that generate the two responses. We have developed transfer approaches that allow us to evaluate whether iABC or GCB derived from ABC or the Ab produced by each in response to by influenza A virus, can provide protection against lethal virus and can effectively neutralize or otherwise clear infection with influenza. We will also examine ABC potential in the context of the elderly host. If we find the aged ABC make a strong contribution to immunity in otherwise compromised aged hosts, it will justify future major efforts to harness ABC to provide improved vaccines and immunotherapies for the aged.

摘要：年龄相关的B细胞：专门免疫病原体？