Hyper-metabolic B cells in the spleens of old mice make antibodies with autoimmune specificities.
Hyper-metabolic B cells in the spleens of old mice make antibodies with autoimmune specificities.
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DOI：
10.1186/s12979-021-00222-3
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发表时间：
2021-02-27
期刊：
影响因子：
--
通讯作者：
Blomberg BB
中科院分区：
文献类型：
--
作者：
Frasca D;Romero M;Garcia D;Diaz A;Blomberg BB
衰老与内源性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细胞代谢表型的影响以及对导致保护性抗体和自身免疫抗体分泌的代谢程序的影响尚不清楚。从幼龄和老年小鼠的脾中分离出脾B细胞及其主要亚群卵泡B细胞(FO)和年龄相关B细胞(ABCs)。收集RNA，通过定量聚合酶链式反应检测与内源性炎症和自身免疫抗体产生相关的标志物的表达。用CpG刺激B细胞和B细胞亚群，7d后收集上清液，用ELISA法测定自身免疫抗体的分泌。代谢指标(氧耗率、胞外酸化率和葡萄糖摄取率)使用SeahorsXFP胞外通量分析仪进行。结果发现，ABC亚群的频率和数量随着年龄的增长而增加，代表着最具促炎作用的B细胞亚群，是老年小鼠脾中炎性标志物表达和自身免疫抗体分泌的主要细胞类型。与年轻小鼠和FO B细胞亚群相比，老年小鼠的高炎性ABC也是高代谢的，这一特征不仅需要支持它们更高的炎症标志物RNA表达，还需要支持它们更高的自身免疫抗体分泌。这些结果确定了内源性炎症、代谢和自身免疫B细胞之间的关系，并为理解导致致病B细胞产生的细胞机制提供了可能的方法，这些B细胞是高炎症和高代谢，并分泌具有自身免疫特异性的抗体。
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.
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DOI：
10.4049/jimmunol.1003964
发表时间：
2012-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Frasca D;Romero M;Diaz A;Alter-Wolf S;Ratliff M;Landin AM;Riley RL;Blomberg BB
通讯作者：
Blomberg BB
影响因子：
37.3
作者：
Eastlack SC;Dong S;Ivan C;Alahari SK
通讯作者：
Alahari SK
影响因子：
7.3
作者：
Diskin C;Pålsson-McDermott EM
通讯作者：
Pålsson-McDermott EM
影响因子：
8
作者：
Cai, Q.;Lin, T.;Kamarajugadda, S.;Lu, J.
通讯作者：
Lu, J.
影响因子：
20.3
作者：
Hao, Yi;O'Neill, Patrick;Cancro, Michael P.
通讯作者：
Cancro, Michael P.