The balance between conventional and unconventional T follicular helper cells influences autoreactive B cell responses
Invariant natural killer T (iNKT) cells are activated by glycolipids presented on CD1d. When iNKT cells interact with and activate B cells, they can differentiate into iNKT follicular helper (iNKTfh) cells, and here, we investigate how this, in turn, regulates conventional T follicular helper (Tfh) cells. This is done in an autoimmune model where antibodies are produced against self-antigens relevant to the autoimmune disease systemic lupus erythematosus (SLE). We find a balance between iNKTfh and Tfh cells that directs the B cell response and influences Tfh cell generation. This altered balance also affects the specificities and increases the autoantibody response. We also show that CD1d expression by B cells is essential for iNKTfh cell generation. In conclusion, our data shed light on how T cell help for B cells is divided between conventional and unconventional helper cell populations and how this has an impact on autoreactive B cell responses.
Authors
- Patricia Barral (ORCID: https://orcid.org/0000-0003-4324-8973)
- Almudena R. Ramiro (ORCID: https://orcid.org/0000-0002-7539-3844)
- Mauro Gaya (ORCID: https://orcid.org/0000-0002-7535-8678)
- Marion Moreews (ORCID: https://orcid.org/0000-0002-5116-2443)
- Curtis Cai (ORCID: https://orcid.org/0000-0002-3490-4361)
- Shengduo Pei
- Alberto del Monte Monge
- Guangchun Chen
- Marcus Buggert (ORCID: https://orcid.org/0000-0003-0633-1719)
- Chenfei He (ORCID: https://orcid.org/0000-0003-3373-8450)
- Facundo D. Batista (ORCID: https://orcid.org/0000-0002-1130-9463)
- Quan‐Zhen Li (ORCID: https://orcid.org/0000-0002-7257-0489)
- Mikael C. I. Karlsson (ORCID: https://orcid.org/0000-0001-5582-614X)
- Shan Wang
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- King's College London (GB)
- Aix-Marseille Université (FR)
- The Francis Crick Institute (GB)
- Ragon Institute of MGH, MIT and Harvard (US)
- Karolinska Institutet (SE)
- Integrated Cardio Metabolic Centre (SE)
- Spanish National Centre for Cardiovascular Research (ES)
- Centre d’Immunologie de Marseille-Luminy (FR)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-04-18
- DOI
- https://doi.org/10.1016/j.celrep.2025.115602
- Citations
- 2
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 1.59
Funders
- Karolinska Institutet
- Vetenskapsrådet
- Thailand Science Research and Innovation