GENERATION OF B CELL MEMORY WITH AGING

随着年龄的增长 B 细胞记忆的生成

• 批准号: 2408481
• 负责人: Richard A. Insel
• 金额: $ 7.95万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2408481
• 关键词: B lymphocyte; Haemophilus influenzae vaccines; age difference; aging; enzyme linked immunosorbent assay; gene expression; human subject; humoral immunity; immunoglobulin genes; immunologic memory; laboratory mouse; polymerase chain reaction; radioimmunoassay; telomerase; telomere

Humoral immunity decreases with aging and contributes to the increased incidence and accompanying morbidity and mortality of infections and to the poor immunogenicity of vaccines in this age group. Although there are multiple etiologies of the decreased humoral immunity with aging, intrinsic defects of aged B lymphocytes and their precursors may make an important contribution to defective primary antibody responses, the low affinity antibody response, and poor persistence of memory. We hypothesize that contributing to these defects in aged humans are the poor generation of memory B cells that is associated with limited diversification of antibody responses and low levels of somatic hyper mutation of immunoglobulin(lg)variable (V) region genes and the poor persistence of memory B cells secondary to shortened telomere length that limits their longevity. We have recently developed an approach to activate and recover a diversified human antibody repertoire after immunization that can be analyzed at the molecular level and methods to up regulate expression of telomerase in memory B cells. Using these approaches, we propose to determine whether immunized healthy elderly adults generate diversified antibody repertoire with somatic hyper mutation and memory B cells to the same extent as young adults and to investigate whether telomerase is up-regulatable in- vitro and telomere shortening occurs in-vivo in B lymphocytes of elderly adults. The results should provide insight into the poor humoral immunity that occurs with aging and a background for developing interventions to reverse immunosenescence or improve, vaccines for the elderly.

体液免疫随着年龄的增长而下降，并导致 增加的发病率和伴随的发病率和死亡率 感染和疫苗的免疫原性差，在这个年龄 组虽然有多种病因的减少 体液免疫与衰老、老年人B内在缺陷 淋巴细胞和它们的前体细胞可以使一个重要的 对缺陷性一抗应答的贡献， 亲和力抗体反应和记忆力差。我们 假设导致老年人这些缺陷的原因是 记忆B细胞的不良生成与 抗体应答的多样性有限， 免疫球蛋白（Ig）可变（V）区体细胞超突变 基因和记忆B细胞的持久性差继发于 缩短的端粒长度限制了它们的寿命。我们有 最近开发了一种方法来激活和恢复 免疫后多样化的人抗体库， 在分子水平上进行分析， 记忆B细胞端粒酶的表达。使用这些 方法，我们建议，以确定是否免疫健康 老年人产生多样化的抗体库与体细胞 超突变和记忆B细胞达到与年轻人相同的程度 并研究端粒酶是否在成年人中上调- 端粒缩短发生在体外和体内的B淋巴细胞中， 老年人。研究结果应该能让我们更深入地了解穷人 随着年龄的增长而发生的体液免疫， 开发干预措施以逆转免疫衰老，或 为老年人接种疫苗。