In humans and mice, susceptibility to infections and autoimmunity increases with age due to age-associated changes in innate and adaptive immune responses. Aged innate cells are also less active, leading to decreased naive T- and B-cell responses. Aging innate cells contribute to an overall heightened inflammatory environment. Naive T and B cells undergo cell-intrinsic age-related changes that result in reduced effector and memory responses. However, previously established B- and T-cell memory responses persist with age. One dramatic change is the appearance of a newly recognized population of age-associated B cells (ABCs) that has a unique cluster of differentiation (CD)21^-CD23^- phenotype. Here, we discuss the discovery and origins of the naive phenotype immunoglobulin (Ig)D⁺ versus activated CD11c⁺T-bet⁺ ABCs, with a focus on protective and pathogenic properties. In humans and mice, antigen-experienced CD11c⁺T-bet⁺ ABCs increase with autoimmunity and appear in response to bacterial and viral infections. However, our analyses indicate that CD21^-CD23^- ABCs include a resting, naive, progenitor ABC population that expresses IgD. Similar to generation of CD11c⁺T-bet⁺ ABCs, naive ABC response to pathogens depends on toll-like receptor stimulation, making this a key feature of ABC activation. Here, we put forward a potential developmental map of distinct subsets from putative naive ABCs. We suggest that defining signals that can harness the naive ABC response may contribute to protection against pathogens in the elderly. CD11c⁺T-bet⁺ ABCs may be useful targets for therapeutic strategies to counter autoimmunity.

中文翻译：

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了解年龄相关 B 细胞的异质种群及其对自身免疫和病原体免疫反应的贡献

在人类和小鼠中，由于先天性和适应性免疫反应的年龄相关变化，对感染和自身免疫的易感性随着年龄的增长而增加。老化的先天细胞也不太活跃，导致初始 T 和 B 细胞反应降低。老化的先天细胞导致整体炎症环境加剧。幼稚 T 和 B 细胞经历细胞内在的年龄相关变化，导致效应和记忆反应减少。然而，先前建立的 B 细胞和 T 细胞记忆反应会随着年龄的增长而持续存在。一个显着的变化是出现了新识别的年龄相关 B 细胞 (ABC) 群体，该群体具有独特的分化簇 (CD)21 ^- CD23 ^-表型。在这里，我们讨论了幼稚表型免疫球蛋白 (Ig)D 的发现和起源⁺与激活的 CD11c ⁺ T-bet ⁺ ABCs 相比，重点是保护性和致病性。在人和小鼠中，抗原经历过的 CD11c ⁺ T-bet ⁺ ABCs 会随着自身免疫而增加，并出现对细菌和病毒感染的反应。然而，我们的分析表明 CD21 ^- CD23 ^- ABCs 包括表达 IgD 的静息、幼稚、祖先 ABC 群体。类似于 CD11c ⁺ T-bet ^{+ 的生成}ABCs，对病原体的幼稚 ABC 反应取决于 toll 样受体刺激，这使其成为 ABC 激活的关键特征。在这里，我们从假定的朴素 ABC 中提出了不同子集的潜在发展图。我们建议定义可以利用天真的 ABC 反应的信号可能有助于保护老年人免受病原体的侵害。CD11c ⁺ T-bet ⁺ ABCs 可能是对抗自身免疫的治疗策略的有用目标。