Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. B Cell Biology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1462126

Clones Reactive to Apoptotic Cells and Specific Chemical Adducts Are Prevalent Among Human Thymic B Cells

Provisionally accepted
Andrea Hertel Andrea Hertel 1,2Talita Aguiar Talita Aguiar 1Shunya Mashiko Shunya Mashiko 1Sarah Nuñez Sarah Nuñez 1Carolina Moore Carolina Moore 3Baoshan Gao Baoshan Gao 3Mattea Ausmeier Mattea Ausmeier 1,4Poloumi Roy Poloumi Roy 1Emmanuel Zorn Emmanuel Zorn 1*
  • 1 Department of Medicine, Columbia University Irving Medical Center, Columbia Center for Translational Immunology, New York, NY, United States
  • 2 Medical Clinic and Polyclinic IV, LMU Munich University Hospital, Munich, Bavaria, Germany
  • 3 Transplant Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
  • 4 Institute of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University of Halle-Wittenberg, Halle (Saale), Germany

The final, formatted version of the article will be published soon.

    Thymus resident B cells were described more than 40 years ago. In early human life, these cells are found predominantly in the medulla and overwhelmingly display an unswitched IgM+ phenotype. The reactivity of thymic IgM B cells, however, is still unclear. Here, we generated 120 IgM-producing B cell clones from 3 separate thymus specimens obtained from infant, adolescent, and adult donors. Using flow cytometry and a unique high-dimensional ELISA platform, we investigated the clones' reactivity to apoptotic cells as well as to common chemical adducts exposed on modified amino acids and other macromolecules. Regardless of the age, approximately 30-40 % of thymic IgM B cells reacted to apoptotic cells. Further, 30-40% displayed reactivity to at least one adduct, including malondialdehyde, Homocysteine, and NEDD 8. Four distinct reactivity patterns were identified through this profiling. Notably, a significant association was observed between reactivity to apoptotic cells, and to one or more adducts, suggesting that the same determinants were recognized in both assays. Additionally, thymic IgM B cells reactive to adducts were more likely to recognize intra-nuclear or intracytoplasmic structures in Hep-2 cells as revealed by immunofluorescence staining. Collectively, our findings suggest that thymic IgM B cells actively uptake apoptotic bodies and cellular debris in the medulla by binding specific chemical adducts. This mechanism could underpin their antigen-presenting function and further support their role in T-cell negative selection.

    Keywords: Thymic B cells, Chemical adducts, natural antibodies, apoptotic cells, Polyreactivity. (Min. 5-Max. 8)

    Received: 09 Jul 2024; Accepted: 02 Oct 2024.

    Copyright: © 2024 Hertel, Aguiar, Mashiko, Nuñez, Moore, Gao, Ausmeier, Roy and Zorn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Emmanuel Zorn, Department of Medicine, Columbia University Irving Medical Center, Columbia Center for Translational Immunology, New York, NY, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.