Obesity accelerates age defects in B cells, and weight loss improves B cell function.
Obesity accelerates age defects in B cells, and weight loss improves B cell function.
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DOI：
10.1186/s12979-023-00361-9
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发表时间：
2023-07-17
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影响因子：
--
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中科院分区：
文献类型：
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我们之前的研究表明，肥胖会加速与年龄相关的B细胞功能缺陷和抗体产生，导致保护性抗体分泌减少和自身免疫增强。我们想评估参加自愿减肥计划的肥胖成人是否具有与瘦成人相似的更高的保护性和更低的自身免疫抗体反应。实验使用的血液分离自已建立的女性瘦成人和老年人人群，以及肥胖女性成年人的血液，在自愿减肥计划之前和之后，他们的身体质量指数（BMI）在12个月内降低了10-34%。所有的参与者都接种了三价灭活流感疫苗。评估血清样本是否存在促炎细胞因子和脂肪因子、疫苗特异性抗体和自身免疫抗体。我们通过流式细胞术评估B细胞池的组成，qPCR评估类开关转录因子和促炎标志物RNA的表达，促炎和抗炎细胞因子的体外分泌及其诱导促炎T细胞的能力。与衰老类似，肥胖会导致血清中促炎细胞因子和自身免疫抗体水平升高，而疫苗特异性抗体水平降低。与血清结果一致，肥胖成人和老年人的B细胞池中富含促炎B细胞亚群，其特征是与细胞衰老相关的标记物表达较高，自身免疫抗体转录因子T-bet水平较高，与流感疫苗保护性反应相关的转录因子E47水平较低。来自肥胖成年人和老年人的B细胞也能够分泌炎性细胞因子，并支持炎性T细胞的产生。肥胖个体B细胞的所有这些促炎特征都因体重减轻而显著减弱，但没有完全逆转。虽然我们的小型观察性研究结果表明，肥胖诱导的功能失调的B细胞反应，类似于衰老过程中发生的反应，在一些肥胖个体中得到改善，但不是所有肥胖个体在减肥后都得到改善，但体重减轻对机制途径的影响在很大程度上是缺失的，值得进一步研究。
We have previously shown that obesity accelerates age-associated defects in B cell function and antibody production leading to decreased secretion of protective antibodies and increased autoimmunity. We wanted to evaluate if obese adults enrolled in a voluntary weight reduction program had higher protective and lower autoimmune antibody responses similar to those observed in lean adults. Experiments were performed using blood isolated from an established cohort of female lean adult and elderly individuals, as well as from the blood of female adults with obesity, before and after a voluntary weight reduction program in which their Body Mass Index (BMI) was reduced 10–34% in 12 months. All participants were vaccinated with the Trivalent Inactivated Influenza vaccine. Serum samples were evaluated for the presence of pro-inflammatory cytokines and adipokines, vaccine-specific antibodies and autoimmune antibodies. We evaluated the composition of the B cell pool by flow cytometry, the expression of RNA for class switch transcription factors and pro-inflammatory markers by qPCR, the in vitro secretion of pro- and anti-inflammatory cytokines and their capacity to induce pro-inflammatory T cells. Obesity, similar to aging, induced increased serum levels of pro-inflammatory cytokines and autoimmune antibodies, while vaccine-specific antibodies were reduced. In agreement with the serum results, the B cell pool of obese adults and elderly individuals was enriched in pro-inflammatory B cell subsets and was characterized by higher expression of markers associated with cell senescence, higher levels of T-bet, the transcription factor for autoimmune antibodies and lower levels of E47, the transcription factor associated with protective responses to the influenza vaccine. B cells from obese adults and elderly individuals were also able to secrete inflammatory cytokines and support the generation of inflammatory T cells. All these pro-inflammatory characteristics of B cells from obese individuals were significantly attenuated, but not completely reversed, by weight loss. Although the results from our small observational study show that obesity-induced dysfunctional B cell responses, similar to those occurring during aging, are ameliorated in some but not all obese individuals after weight loss, the effects of body weight loss on mechanistic pathways are largely missing and deserve further investigation.
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影响因子：
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作者：
Frasca, Daniela;Romero, Maria;Garcia, Denisse;Diaz, Alain;Blomberg, Bonnie B.
通讯作者：
Blomberg, Bonnie B.
影响因子：
7.3
作者：
Frasca D;Blomberg BB
通讯作者：
Blomberg BB
影响因子：
16.6
作者：
通讯作者：
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DOI：
10.1146/annurev-cellbio-011620-034148
发表时间：
2020-10-06
影响因子：
11.3
作者：
Frasca D;Diaz A;Romero M;Garcia D;Blomberg BB
通讯作者：
Blomberg BB
影响因子：
4.4
作者：
Frasca, Daniela;Diaz, Alain;Blomberg, Bonnie B.
通讯作者：
Blomberg, Bonnie B.