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Cell Reports, 2022 Sep 20;40(12):111391 | https://doi.org/10.1016/j.celrep.2022.111391 Association of B cell profile and receptor repertoire with the progression of Alzheimer's disease

Jong-Chan Park^1,2,3,4,17, Jinsung Noh^5,13,17, Sukjin Jang^6,17, Ki Hyun Kim^7,8, Hayoung Choi^1,3, Dongjoon Lee^1,3, Jieun Kim¹, Junho Chung^7,8,9, Dong Young Lee^10,11,12, Yonghee Lee⁵, Hyunho Lee⁵, Duck Kyun Yoo^7,9, Amos Chungwon Lee¹³, Min Soo Byun^11,12, Dahyun Yi¹², Sun-Ho Han^1,2,3, Sunghoon Kwon^{5,13,14,15,16}, Inhee Mook-Jung^1,2,3,18

¹Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
²Neuroscience Research Institute, Medical Research Center, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
³SNU Dementia Research Center, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
⁴Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK
⁵Department of Electrical and Computer Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea
⁶Department of Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
⁷Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
⁸Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
⁹Department of Biomedical Science, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
¹⁰Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul 03080, Republic of Korea
¹¹Department of Psychiatry, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
¹²Department of Neuropsychiatry, Seoul National University Hospital, Seoul 03080, Republic of Korea
¹³Bio-MAX Institute, Seoul National University, Seoul 08826, Republic of Korea
¹⁴BK21+ Creative Research Engineer Development for IT, Seoul National University, Seoul 08826, Republic of Korea
¹⁵Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea
¹⁶Interdisciplinary Program in Bioengineering, Seoul National University, Seoul 08826, Republic of Korea

¹⁷These authors contributed equally
¹⁸Lead contact
Corresponding authors: Sun-Ho Han, Sunghoon Kwon, Inhee Mook-Jung

Abstract

Alzheimer’s disease (AD) is the most prevalent type of dementia. Reports have revealed that the peripheral immune system is linked to neuropathology; however, little is known about the contribution of B lymphocytes in AD. For this longitudinal study, 133 participants are included at baseline and second-year follow-up. Also, we analyze B cell receptor (BCR) repertoire data generated from a public dataset of three normal and 10 AD samples and perform BCR repertoire profiling and pairwise sharing analysis. As a result, longitudinal increase in B lymphocytes is associated with increased cerebral amyloid deposition and hyperactivates induced pluripotent stem cell-derived microglia with loss-of-function for beta-amyloid clearance. Patients with AD share similar class-switched BCR sequences with identical isotypes, despite the high somatic hypermutation rate. Thus, BCR repertoire profiling can lead to the development of individualized immune-based therapeutics and treatment. We provide evidence of both quantitative and qualitative changes in B lymphocytes during AD pathogenesis.

논문정보

형식Research article
게재일2022년 09월 (BRIC 등록일 2022-11-08)
연구진국내(교신)+국외 연구진
분야 의약학 > 신경의학

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