Age-Associated B Cells Specialized for Immunity to Pathogens?

综述：乳腺癌相关B细胞：专门针对病原体的免疫？ 随着年龄的增长，来自幼稚CD 4 T细胞的T滤泡辅助细胞和来自滤泡上皮细胞的生发中心B细胞的生成， 产生高亲和力抗体（Ab）所需的B细胞变得受损。最新 老年人的流感疫苗不能有效诱导这些关键反应。故长者， 虽然已经有抗体对生命早期遇到的病原体进行保护，但它们对新的 病毒株（如流感）和新出现的病原体（如COVID-19）。我们注意到， 我们发现，在老年小鼠中，不寻常的分泌抗体的B细胞群体与流感病毒感染有关， 通过刺激最近描述的“年龄相关B细胞”（ABC）。一群流感诱导的ABC （iABC）的产生独立于CD 4 T细胞的帮助，但严格依赖于病原体的刺激- “危险”信号。最近我们发现，当有帮助时，类似GCB的反应可以代替 被诱导并产生浆细胞。我们还发现ABC在无菌小鼠中的发展支持了内在的 与年龄相关的ABC发展的性质。值得注意的是，ABC是主要的幼稚B细胞， 老年小鼠 在这里，我们将定义抗原和病原体识别所需的信号，以及CD 4帮助产生的信号。 这两个答案。我们已经开发了转移方法，使我们能够评估是否iABC或GCB 来源于ABC或由各自响应于甲型流感病毒而产生的Ab，可以提供针对 致命的病毒，并能有效地中和或以其他方式清除流感感染。我们还将检查ABC 在老年人的背景下。如果我们发现老年人的ABC对免疫力有很大的贡献， 否则会受到影响的老化主机，这将证明未来利用ABC提供改进的 老年人的疫苗和免疫疗法。

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.