Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (8): 3668-3676.doi: 10.4103/NRR.NRR-D-23-01942

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Gamma-type immunoglobulin enhances phagocytosis of amyloid-beta fibrils by microglia

Tian Zhou1, 2, 3, *, Yue Zhong2, 4, Shoujun Yu2, Ruibing Sun5, Zhenwei Zhang6, 7, Xiaoyan Du6, 7, Simon Ming-Yuen Lee8, Zhitong Chen2, 9, Weiming Tian10, Yuxiao Lai2, 9, Bing Song2, 4, *, Yiming Zheng6, 7, *, Zhen Xu2, *, †   

  1. 1Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong- Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province, China; 
    2Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong Province, China; 
    3Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong Province, China; 
    4Department of Dermatology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China; 
    5Department of Ophthalmology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong Province, China; 
    6State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Department of Neurology, Xiang’an Hospital of Xiamen University, Xiamen University, Xiamen, Fujian Province, China; 
    7Shenzhen Research Institute of Xiamen University, Shenzhen, Guangdong Province, China; 
    8Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hong Kong Special Administration Region, China; 
    9National Innovation Center for Advanced Medical Devices, Shenzhen, Guangdong Province, China; 
    10School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang Province, China

  • Online:2026-08-18 Published:2026-04-27
  • Contact: Tian Zhou, PhD, tianzhou_tz@163.com; Bing Song, MD, PhD, bing.song@siat.ac.cn; Yiming Zheng, PhD, ymzheng@xmu.edu.cn; Zhen Xu, PhD, zhen.xu@siat.ac.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 82171082 (to ZX), 32000727 (to TZ), 32370731 (to YZ); Guangdong Basic and Applied Basic Research Foundation, No. 2024A151501069 (to ZX); Shenzhen Science and Technology Program, Nos. JCYJ20210324101603009 (to ZX), GJHZ20220913142807015 (to TZ), JCYJ20220531100204010 (to TZ), JCYJ20230807091308018 (to YZ); and Shenzhen Medical Research Funds, No. A2303068 (to TZ).

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Abstract: The peripheral immune system has emerged as a regulator of neurodegenerative diseases such as Alzheimer’s disease. Microglia are resident immune cells in the brain that may orchestrate communication between the central nervous system and peripheral immune system, though the mechanisms are unclear. Here, we found that gamma-type immunoglobulin, a product originating from peripheral blood B cells, localized in the brain parenchyma of multiple mouse models with amyloid pathology, and was enriched on microglia but not on other brain cell types. Further experiments showed that gamma-type immunoglobulin bound to microglial cell membranes and led to diverse transcriptomic changes, including upregulation of pathways related to phagocytosis and immunity. Functional assays demonstrated that gamma-type immunoglobulin enhanced microglial phagocytic capacity for amyloid-beta fibrils via its Fc, but not Fab, fragment. Our data indicate that microglia, when exposed to gamma-type immunoglobulin, exhibit an enhanced capacity for clearing amyloid-beta fibrils, potentially via the gamma-type immunoglobulin Fc fragment signaling pathway. This suggests that parenchymal gamma-type immunoglobulin should be further investigated to determine whether it may play a beneficial role against Alzheimer’s disease by enhancing microglial function.

Key words: adaptive immunity, Alzheimer’s disease, amyloid-beta, B cell, blood–brain barrier, cell membrane, Fc fragment, gamma-type immunoglobulin, microglia, phagocytosis