Twin study dissects CXCR3+ memory B cells as non-heritable feature in multiple sclerosis

Florian Ingelfinger, Kirsten L Kuiper, Can Ulutekin, Lukas Rindlisbacher, Sarah Mundt, Lisa Ann Gerdes, Joost Smolders, Marvin M van Luijn, Burkhard Becher*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: 

In multiple sclerosis (MS), B cells are considered main triggers of the disease, likely as the result of complex interaction between genetic and environmental risk factors. Studies on monozygotic twins discordant for MS offer a unique way to reduce this complexity and reveal discrepant subsets.

METHODS: 

In this study, we analyzed B cell subsets in blood samples of monozygotic twins with and without MS using publicly available data. We verified functional characteristics by exploring the role of therapy and performed separate analyses in unrelated individuals.

FINDINGS: 

The frequencies of CXCR3+ memory B cells were reduced in the blood of genetically identical twins with MS compared to their unaffected twin siblings. Natalizumab (anti-VLA-4 antibody) was the only treatment regimen under which these frequencies were reversed. The CNS-homing features of CXCR3+ memory B cells were supported by elevated CXCL10 levels in MS cerebrospinal fluid and their in vitro propensity to develop into antibody-secreting cells.

CONCLUSIONS: 

Circulating CXCR3+ memory B cells are affected by non-heritable cues in people who develop MS. This underlines the requirement of environmental risk factors such as Epstein-Barr virus in triggering these B cells. We propose that after CXCL10-mediated entry into the CNS, CXCR3+ memory B cells mature into antibody-secreting cells to drive MS.


Original languageEnglish
Pages (from-to)368-373.e3
JournalMed
Volume5
Issue number4
Early online date25 Mar 2024
DOIs
Publication statusPublished - 12 Apr 2024

Bibliographical note

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

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