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ResearchIn-Press PreviewImmunology Open Access | 10.1172/jci.insight.172006

Autoreactive B cells in rheumatoid arthritis include mainly activated CXCR3+ memory B cells and plasmablasts

Sanne Reijm,1 Joanneke C. Kwekkeboom,1 Nienke J. Blomberg,1 Jolien Suurmond,1 Diane Van der Woude,2 Rene E.M. Toes,2 and Hans Ulrich Scherer2

1Leiden University Medical Center (LUMC), Leiden, Netherlands

2Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden, Netherlands

Find articles by Reijm, S. in: JCI | PubMed | Google Scholar |

1Leiden University Medical Center (LUMC), Leiden, Netherlands

2Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden, Netherlands

Find articles by Kwekkeboom, J. in: JCI | PubMed | Google Scholar

1Leiden University Medical Center (LUMC), Leiden, Netherlands

2Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden, Netherlands

Find articles by Blomberg, N. in: JCI | PubMed | Google Scholar

1Leiden University Medical Center (LUMC), Leiden, Netherlands

2Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden, Netherlands

Find articles by Suurmond, J. in: JCI | PubMed | Google Scholar |

1Leiden University Medical Center (LUMC), Leiden, Netherlands

2Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden, Netherlands

Find articles by Van der Woude, D. in: JCI | PubMed | Google Scholar |

1Leiden University Medical Center (LUMC), Leiden, Netherlands

2Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden, Netherlands

Find articles by Toes, R. in: JCI | PubMed | Google Scholar |

1Leiden University Medical Center (LUMC), Leiden, Netherlands

2Department of Rheumatology, Leiden University Medical Center (LUMC), Leiden, Netherlands

Find articles by Scherer, H. in: JCI | PubMed | Google Scholar |

Published September 19, 2023 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.172006.
Copyright © 2023, Reijm et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published September 19, 2023 - Version history
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Abstract

Many autoimmune diseases (AIDs) are characterized by persistence of autoreactive B cell responses which is often directly implicated in disease pathogenesis. How and why these cells are generated or how they are maintained for years is largely unknown. Rheumatoid arthritis is among the most common AIDs and characterized by autoantibodies recognizing proteins with post-translational modifications (PTMs). This PTM-directed, autoreactive B cell compartment is ill defined. Here, we visualized the B cell response against the three main types of PTM antigens implicated in RA by spectral flow cytometry. Our results showed extensive cross-reactivity of PTM-directed B cells against all three PTM antigens (citrulline, homocitrulline and acetyllysine). Unsupervised clustering revealed several distinct memory B cell (mBC) populations. PTM-directed cells clustered with the most recently activated, class-switched mBC phenotype, expressing high CD80, low CD24 and low CD21. Notably, patients also harbored large fractions of PTM-directed plasmablasts (PB). Both PTM-directed mBC and PB showed high expression of CXCR3, a receptor for chemokines abundantly present in arthritic joints. Together, our data provide detailed insight into the biology of B cell autoreactivity and its remarkable, seemingly exhaustless persistence in a prominent human AID.

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  • Version 1 (September 19, 2023): In-Press Preview
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