近日，中山大学徐春亮教授团队的论文发现了禁食通过β-羟基丁酸介导的浆细胞耗竭损害体液免疫记忆。这一研究成果于2026年2月23日发表在国际顶尖学术期刊《免疫学》上。

小组在人类和母鼠模型中表明，间歇性禁食通过加速抗体衰变来损害体液免疫记忆。在小鼠中，禁食选择性地消耗LLPCs，同时保留MBCs。在机制上，这种作用是由细胞外β-羟基丁酸增加介导的，β-羟基丁酸是禁食期间产生的一种酮体，通过对浆细胞的羟基羧酸受体2（HCAR2）起作用。β-羟基丁酸激活HCAR2-Gαi腺苷酸环化酶-cAMP轴下调CXCR4，导致浆细胞退出骨髓生态位并在周围发生凋亡。这些发现表明，禁食诱导的代谢信号调节体液免疫持续时间，并提示饮食和生活方式可能影响疫苗的有效性。

据介绍，由记忆B细胞（MBCs）和长寿命浆细胞（LLPCs）介导的体液免疫记忆对于感染或疫苗接种后的持续保护至关重要。LLPCs通过长时间分泌保护性中和抗体来保护宿主。然而，调节它们生存的机制和它们的保护性抗体的持久性仍不清楚。

附：英文原文

Title: Fasting impairs humoral immunological memory by β-hydroxybutyrate-mediated depletion of plasma cells

Author: Yiming Zhu, Baoshan Ding, Haimei Lv, Hui Xu, Jiamei Chen, Juan Xu, Qian Wu, Xiaoxiao Hao, Yunqi Hu, Jian Guo, Jun Chen, Chaofeng Liang, Yuzhuang Li, Jiawen Wu, Nan Cao, Jijun Zhao, Guangwen Ren, Hua Jin, Yiwen Zhang, Yiping Li, Hui Zhang, Chunliang Xu

Issue&Volume: 2026-02-23

Abstract: Humoral immunological memory mediated by memory B cells (MBCs) and long-lived plasma cells (LLPCs) is critical for sustained protection following infection or vaccination. LLPCs protect the hosts by secreting protective neutralizing antibodies over extended periods. However, the mechanism regulating their survival and thus the durability of protective antibodies remains unclear. Here, we showed in human and mouse models that intermittent fasting impaired humoral immunological memory by accelerating antibody decay. Fasting selectively depleted LLPCs while sparing MBCs in mice. Mechanistically, this effect was mediated by increased extracellular β-hydroxybutyrate, a ketone body produced during fasting, which acted through the hydroxycarboxylic acid receptor 2 (HCAR2) on plasma cells. Activation of the HCAR2-Gαi-adenylate cyclase-cAMP axis by β-hydroxybutyrate downregulated CXCR4, leading plasma cells to exit their bone marrow niche and undergo apoptosis in the periphery. These findings reveal that fasting-induced metabolic signals regulate humoral immunity duration and suggest that diet and lifestyle could influence vaccine effectiveness.

DOI: 10.1016/j.immuni.2026.01.002

Source: https://www.cell.com/immunity/abstract/S1074-7613(26)00003-8