Aging is associated with increased intrinsic B cell inflammation, decreased protective antibody responses and increased autoimmune antibody responses. The effects of aging on the metabolic phenotype of B cells and on the metabolic programs that lead to the secretion of protective versus autoimmune antibodies are not known. Splenic B cells and the major splenic B cell subsets, Follicular (FO) and Age-associated B cells (ABCs), were isolated from the spleens of young and old mice and left unstimulated. The RNA was collected to measure the expression of markers associated with intrinsic inflammation and autoimmune antibody production by qPCR. B cells and B cell subsets were also stimulated with CpG and supernatants collected after 7 days to measure autoimmune IgG secretion by ELISA. Metabolic measures (oxygen consumption rate, extracellular acidification rate and glucose uptake) were performed using a Seahorse XFp extracellular flux analyzer. Results have identified the subset of ABCs, whose frequencies and numbers increase with age and represent the most pro-inflammatory B cell subset, as the cell type mainly if not exclusively responsible for the expression of inflammatory markers and for the secretion of autoimmune antibodies in the spleen of old mice. Hyper-inflammatory ABCs from old mice are also hyper-metabolic, as compared to those from young mice and to the subset of FO B cells, a feature needed not only to support their higher expression of RNA for inflammatory markers but also their higher autoimmune antibody secretion. These results identify a relationship between intrinsic inflammation, metabolism and autoimmune B cells and suggest possible ways to understand cellular mechanisms that lead to the generation of pathogenic B cells, that are hyper-inflammatory and hyper-metabolic, and secrete IgG antibodies with autoimmune specificities.

中文翻译：

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年老小鼠脾脏中代谢亢进的 B 细胞可产生具有自身免疫特异性的抗体


衰老与内在 B 细胞炎症增加、保护性抗体反应减少和自身免疫抗体反应增加有关。衰老对 B 细胞代谢表型以及导致分泌保护性抗体和自身免疫抗体的代谢程序的影响尚不清楚。从年轻和年老小鼠的脾脏中分离出脾 B 细胞和主要的脾 B 细胞亚群、滤泡 (FO) 和年龄相关 B 细胞 (ABC)，并且未受刺激。收集 RNA 以通过 qPCR 测量与内在炎症和自身免疫抗体产生相关的标记物的表达。 B 细胞和 B 细胞亚群也用 CpG 刺激，7 天后收集上清液，通过 ELISA 测量自身免疫 IgG 分泌。使用 Seahorse XFp 细胞外通量分析仪进行代谢测量（耗氧率、细胞外酸化率和葡萄糖摄取）。结果确定了 ABC 子集，其频率和数量随着年龄的增长而增加，代表最具促炎性的 B 细胞子集，该细胞类型主要（如果不是唯一）负责炎症标志物的表达和自身免疫抗体的分泌。老小鼠的脾脏。与年轻小鼠和 FO B 细胞亚群相比，年老小鼠的高炎症 ABC 也具有高代谢性，这一特征不仅支持其炎症标记物 RNA 的较高表达，而且还支持其较高的自身免疫抗体分泌。 这些结果确定了内在炎症、代谢和自身免疫 B 细胞之间的关系，并提出了了解导致致病性 B 细胞产生的细胞机制的可能方法，这些 B 细胞具有高炎症和高代谢性，并分泌具有自身免疫特异性的 IgG 抗体。