Effect of Age on Antibody Diversity

年龄对抗体多样性的影响

• 批准号: 10913145
• 负责人: PATRICIA J GEARHART
• 金额: $ 33.3万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10913145
• 关键词: Alzheimer' s Disease; Antibodies; Antibody Diversity; Antibody Response; Antigens; B-Lymphocytes; Brain; Development; Female; Frequencies; Immunoglobulin Class Switching; Immunoglobulin Somatic Hypermutation; Immunoglobulins; Impaired cognition; Inflammation; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A virus; Influenza vaccination; Methods; Mus; Pathogenicity; Play; Prevention; Production; Role; Severity of illness; Structure of germinal center of lymph node; age effect; improved; male; mutant; novel; response; single-cell RNA sequencing; universal influenza vaccine

For antibody responses in mice, compared with males, inactivated influenza vaccination of 34 female mice causes greater production of class-switched, somatically-hypermutated antibodies and a more robust germinal center B cell response, leading to more diverse H1N1 antigen recognition and better protection against mutant influenza A viruses. Harnessing methods to improve GC B cell responses and frequencies of somatic hypermutations, especially in males, should be considered in the development of universal influenza vaccines. For Alzheimer's disease, we plan to perform a systematic analysis of B cells in the brains of AD mice. Using single-cell RNAseq and immunoglobulin repertoire analysis, B cells will be examined to identify changes in quantity and function in relation to cognitive decline.

对于小鼠中的抗体应答，与雄性相比，34只雌性小鼠的灭活流感疫苗接种导致产生更多的类别转换、体细胞高度突变的抗体和更稳健的生发中心B细胞应答，从而导致更多样化的H1N1抗原识别和更好的针对突变型甲型流感病毒的保护。在开发通用流感疫苗时，应考虑利用方法来改善GC B细胞应答和体细胞超突变频率，特别是在男性中。对于阿尔茨海默病，我们计划对AD小鼠大脑中的B细胞进行系统分析。使用单细胞RNAseq和免疫球蛋白库分析，将检查B细胞以鉴定与认知下降相关的数量和功能变化。

项目成果

Signals that drive T-bet expression in B cells.

• DOI: 10.1016/j.cellimm.2017.09.004
• 发表时间: 2017-11
• 期刊: Cellular immunology
• 影响因子: 4.3
• 作者: Myles A;Gearhart PJ;Cancro MP
• 通讯作者: Cancro MP

Commentary for the Special Issue on 'Aging and Sex in Immunity'.

“免疫中的衰老和性”特刊评论。

• DOI: 10.1016/j.cellimm.2019.104037
• 发表时间: 2020
• 期刊: Cellular immunology
• 影响因子: 4.3
• 作者: Klein,SabraL;Gearhart,PatriciaJ
• 通讯作者: Gearhart,PatriciaJ