Obesity decreases B cell responses in young and elderly individuals.
Obesity decreases B cell responses in young and elderly individuals.
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DOI：
10.1002/oby.21383
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Blomberg BB
中科院分区：
文献类型：
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作者：
Frasca D;Ferracci F;Diaz A;Romero M;Lechner S;Blomberg BB
评估肥胖相关炎症对流感疫苗应答的影响。我们测量了年轻人和老年人，包括瘦的和肥胖的，对流感疫苗的抗体反应。我们发现体内疫苗反应、循环转换记忆和过渡B细胞减少，促炎晚期/耗竭记忆B细胞增加。体外B细胞功能通过活化诱导的胞苷脱氨酶（AID）和E47（最佳抗体应答的标志物）测定。此外，在肥胖个体的B细胞培养物中，IL-6的产生增加，而IL-10的产生减少。未受刺激的B细胞中的免疫活化标志物（TNF-α、TLR 4、micro-RNA）也被发现增加，并且与B细胞功能呈负相关。为了揭示潜在的机制，我们在体外用瘦素刺激瘦个体的B细胞，肥胖时脂肪因子增加。瘦素增加磷酸化STAT 3，这对TNF-α的产生至关重要，并减少磷酸化AMPK，磷酸化p38 MAPK和E47上游的能量传感酶。瘦素诱导的磷酸化STAT 3和磷酸化AMPK水平与肥胖个体的B细胞中的水平相似。这些结果表明，瘦素可能是导致肥胖症B细胞功能下降的原因。
To evaluate the effects of obesity-associated inflammation on influenza vaccine responses. We measured in young and elderly individuals, both lean and with obesity, antibody responses to influenza vaccination. We found a decrease in in vivo vaccine responses, circulating switched memory and transitional B cells and an increase in pro-inflammatory late/exhausted memory B cells. In vitro B cell function was measured by activation-induced cytidine deaminase (AID) and E47, markers of optimal antibody responses. Moreover, IL-6 production was increased, whereas IL-10 production was decreased, in cultures of B cells from individuals with obesity. Markers of immune activation (TNF-α, TLR4, micro-RNAs) in unstimulated B cells were also found increased and were negatively correlated with B cell function. In order to reveal potential mechanisms, we stimulated B cells from lean individuals in vitro with leptin, the adipokine increased in obesity. Leptin increased phospho-STAT3, crucial for TNF-α production, and decreased phospho-AMPK, the energy sensing enzyme upstream of phospho-p38 MAPK and E47. Leptin-induced phospho-STAT3 and phospho-AMPK levels were similar to those in B cells from individuals with obesity. These results demonstrate that leptin can be responsible for decreased B cell function in obesity.