Age-related changes in antigen-specific natural antibodies are influenced by sex.
Age-related changes in antigen-specific natural antibodies are influenced by sex.
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抗原特异性天然抗体的年龄相关变化受到性别的影响。
DOI：
10.3389/fimmu.2022.1047297
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
来源于CD 5 + B-1细胞的天然抗体（NA B）可维持组织稳态，控制炎症，帮助建立针对病原体的长期保护性应答，并提供立即保护免受感染。CD 5 + B-1细胞NAb识别在细菌和衰老红细胞上发现的进化上固定的表位，例如磷脂酰胆碱（PtC）。抗PtC抗体在预防细菌性脓毒症中是必不可少的。CD 5 + B-1细胞衍生的NAb具有独特的生殖系样结构，其缺乏N-添加，这是提供抗感染保护的关键特征。以前，我们证明了从雄性小鼠获得的PtC+ CD 5 + B-1细胞IgM的库和种系状态随年龄的变化取决于B-1细胞的解剖位置。最近，我们证明了来自老年雌性小鼠的血清抗体保持对肺炎球菌感染的保护，而来自雄性小鼠的血清抗体不提供保护。在这里，我们表明，老年雌性小鼠有显着更多的脾脏PtC+ CD 5 + B-1细胞和更多的PtC特异性血清IgM比老年雄性小鼠。此外，当比较PtC+ CD 5 + B-1细胞的B细胞受体（BCR）测序结果时，我们发现年龄和生物性别相关的库差异。虽然老年雄性和雌性小鼠的PtC+ CD 5 + B-1细胞的BCR生殖系状态在腹腔中相似，但在脾脏中存在显著差异，老年雌性小鼠保留生殖系构型，而老年雄性小鼠则不保留。核酸感应toll样受体在维持PtC+ B-1细胞中至关重要;因此，为了开始理解在雄性和雌性PtC+ CD 5 + B-1细胞库之间观察到的差异的机制，我们分析了无细胞核酸的水平，发现老年雌性中的增加。我们的研究结果表明，老年男性和女性之间的抗原环境不同，导致随着时间的推移，抗原特异性B-1细胞的差异选择。进一步阐明生物学性别差异如何影响B-1细胞在老化环境中的维持，对于了解细菌感染易感性中与性别和年龄相关的差异至关重要，并将有助于开发更有效的疫苗接种和/或针对男性和女性的治疗策略。
Natural antibody (NAb) derived from CD5+ B-1 cells maintains tissue homeostasis, controls inflammation, aids in establishing long-term protective responses against pathogens, and provides immediate protection from infection. CD5+ B-1 cell NAbs recognize evolutionarily fixed epitopes, such as phosphatidylcholine (PtC), found on bacteria and senescent red blood cells. Anti-PtC antibodies are essential in protection against bacterial sepsis. CD5+ B-1 cell-derived NAbs have a unique germline-like structure that lacks N-additions, a feature critical for providing protection against infection. Previously, we demonstrated the repertoire and germline status of PtC+CD5+ B-1 cell IgM obtained from male mice changes with age depending on the anatomical location of the B-1 cells. More recently, we demonstrated serum antibody from aged female mice maintains protection against pneumococcal infection, whereas serum antibody from male mice does not provide protection. Here, we show that aged female mice have significantly more splenic PtC+CD5+ B-1 cells and more PtC specific serum IgM than aged male mice. Furthermore, we find both age and biological sex related repertoire differences when comparing B cell receptor (BCR) sequencing results of PtC+CD5+ B-1 cells. While BCR germline status of PtC+CD5+ B-1 cells from aged male and female mice is similar in the peritoneal cavity, it differs significantly in the spleen, where aged females retain germline configuration and aged males do not. Nucleic acid sensing toll-like receptors are critical in the maintenance of PtC+ B-1 cells; therefore, to begin to understand the mechanism of differences observed between the male and female PtC+CD5+ B-1 cell repertoire, we analyzed levels of cell-free nucleic acids and found increases in aged females. Our results suggest the antigenic milieu differs between aged males and females, leading to differential selection of antigen-specific B-1 cells over time. Further elucidation of how biological sex differences influence the maintenance of B-1 cells within the aging environment will be essential to understand sex and age-related disparities in the susceptibility to bacterial infection and will aid in the development of more effective vaccination and/or therapeutic strategies specific for males and females.