B cells shed light on diminished vaccine responses in obesity.
B cells shed light on diminished vaccine responses in obesity.
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B 细胞揭示了肥胖症中疫苗反应减弱的情况。
DOI：
10.1002/oby.21429
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Nikolajczyk,BarbaraS
中科院分区：
文献类型：
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作者：
Nicholas,DequinaA;Nikolajczyk,BarbaraS
肥胖导致的免疫功能受损是一个日益严重的公共卫生问题。免疫细胞的慢性炎症支持肥胖相关的代谢功能障碍，较低的疫苗效力表明了肥胖者免疫紊乱的重要性(1，2)。然而，很少有研究确定肥胖改变免疫细胞执行其生殖器任务的能力的机制：清除病原体。尽管许多临床研究支持肥胖时免疫反应受到干扰的观点，但该领域对肥胖相关免疫反应中的髓系细胞(单核/巨噬细胞、树突状细胞)和T细胞的偏向关注淡化了B细胞的关键重要性及其产生病原体中和抗体的独特能力。一些研究表明，B细胞通过促炎细胞因子、糖尿病抗体或支持T细胞炎症的能力来促进肥胖引起的炎症(参考文献1)。在这一期的肥胖症中，Frasca等人(4)证明了炎性B细胞，基于构成肿瘤坏死因子α的产生(5)，具有受损的功能，通过肥胖者早期(~4周)流感特异性抗体的产生来衡量，无论年龄。作者利用这些发现为B细胞优化的分子机制中与肥胖相关的缺陷提供了新的见解。肥胖者未受刺激的B细胞中的这些缺陷反映了衰老，肥胖与衰老相关的缺陷复合。作者的发现与已发表的研究结果相反，后者显示肥胖者的早期抗流感抗体反应与瘦人相似(甚至略有增加)(1，6)。然而，随访分析显示，肥胖者12个月时的抗流感抗体效价显著降低(1)，这表明记忆B细胞产生的缺陷类似于Frasca等人证明的缺陷(4)。因此，这些研究之间的差异是肥胖削弱早期免疫反应的能力与接种疫苗后紧随其后的流感季节最相关。对这种差异的一个合理解释是，Sheridan等人(1)在最初1-2年内对疫苗中包含的三种疫苗毒株中的每一种进行了个体反应分析，而Frasca等人(4)总结了对疫苗的混合反应，其中一种毒株连续三到四个流感季节包括在疫苗中。
Compromised immune function due to obesity is a growing public health concern. Chronic inflammation from immune cells supports obesity-associated metabolic dysfunction, and lower vaccine efficacy suggests the importance of immune perturbations in people with obesity (1, 2). However, few studies have identified mechanisms by which obesity modifies the ability of immune cells to perform their seminal task: pathogen clearance. Although numerous clinical studies have supported the idea that immune responses are perturbed in obesity, a skewed focus of the field on myeloid cells (monocytes/macrophages, dendritic cells) and T cells in obesity-associated immune responses downplays the critical importance of B cells and their unique ability to produce pathogen-neutralizing antibodies. A handful of studies show that B cells promote obesity-induced inflammation through a pro-inflammatory cytokine profile, diabetogenic antibodies, or an ability to support T cell inflammation (Ref. 3 and references therein), but the vast majority of studies do little to address the relationship between altered B cell (or other immune cell) responses and defective pathogen clearance in obesity.In this issue of Obesity, Frasca et al.(4) demonstrate that inflammatory B cells, identified based on constitutive TNFα production (5), have compromised function, as measured by early (~ 4 weeks) flu-specific antibody production in subjects with obesity, regardless of age. The authors take advantage of these findings to provide novel insights into obesityassociated defects in the molecular machinery of B cell optimization. These defects in unstimulated B cells from individuals with obesity mirror aging, with obesity compounding aging-associated deficiencies. The authors’ findings contrast with published work, which showed early anti-flu antibody responses are similar (or even slightly increased) in subjects with obesity compared to lean subjects (1, 6). However, follow-up analysis showed anti-flu antibody titers at 12 months were significantly lower in subjects with obesity (1), suggesting defects in memory B cell production akin to defects demonstrated by Frasca et al.(4). Therefore, the disparity among the studies is the ability of obesity to blunt early immune responses most relevant to the flu season that immediately follows vaccination. One reasonable explanation for this discrepancy is that Sheridan et al.(1) assayed individual responses to each of three vaccine strains in the first 1–2 years in which those strains were included in the vaccine, while Frasca et al.(4) summarized the mixed response to vaccine, with one of the strains included in the vaccine for three to four consecutive flu seasons.