Publication: The balance between conventional and unconventional T follicular helper cells influences autoreactive B cell responses

Published in:

Authors: Chenfei He, Shan Wang, Marion Moreews, Shengduo Pei, Guangchun Chen, Quan-Zhen Li, Alberto del Monte Monge, Almudena R Ramiro, Curtis Cai, Mauro Gaya, Patricia Barral, Marcus Buggert, Facundo D Batista, Mikael C.I. Karlsson

Summary

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.

Link to Pubmed [PMID] – 40252220

Link to HAL – amu-05515367

Link to DOI – 10.1016/j.celrep.2025.115602