Association of B cell profile and receptor repertoire with the progression of Alzheimer's disease

Jong-Chan Park; Jinsung Noh; Sukjin Jang; Ki Hyun Kim; Hayoung Choi; Dongjoon Lee; Jieun Kim; Junho Chung; Dong Young Lee; Yonghee Lee; Hyunho Lee; Duck Kyun Yoo; Amos Chungwon Lee; Min Soo Byun; Dahyun Yi; Sun-Ho Han; Sunghoon Kwon; Inhee Mook-Jung

doi:10.1016/j.celrep.2022.111391

Association of B cell profile and receptor repertoire with the progression of Alzheimer's disease

Cell Rep. 2022 Sep 20;40(12):111391. doi: 10.1016/j.celrep.2022.111391.

Authors

Jong-Chan Park¹, Jinsung Noh², Sukjin Jang³, Ki Hyun Kim⁴, Hayoung Choi⁵, Dongjoon Lee⁵, Jieun Kim⁶, Junho Chung⁷, Dong Young Lee⁸, Yonghee Lee⁹, Hyunho Lee⁹, Duck Kyun Yoo¹⁰, Amos Chungwon Lee¹¹, Min Soo Byun¹², Dahyun Yi¹³, Sun-Ho Han¹⁴, Sunghoon Kwon¹⁵, Inhee Mook-Jung¹⁶

Affiliations

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

PMID: 36130492
DOI: 10.1016/j.celrep.2022.111391

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.

Keywords: Alzheimer’s disease; B cell receptor repertoire; B lymphocyte; CP: Immunology; CP: Neuroscience; Pittsburgh compound B; cerebral amyloid deposition; immunoglobulin G; induced pluripotent stem cell; microglia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / metabolism
Amyloid beta-Peptides / metabolism
B-Lymphocytes / metabolism
Humans
Longitudinal Studies
Receptors, Antigen, B-Cell

Substances

Amyloid beta-Peptides
Receptors, Antigen, B-Cell