He, ChenfeiWang, ShanMoreews, MarionPei, ShengduoChen, GuangchunLi, Quan-ZhenDel Monte Monge, AlbertoRamiro, Almudena RCai, CurtisGaya, MauroBarral, PatriciaBuggert, MarcusBatista, Facundo DKarlsson, Mikael C I2025-12-162025-12-162025-05-27Cell Rep. 2025 May 27;44(5):115602.https://hdl.handle.net/20.500.12105/27058Invariant 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.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/CD1dCP: ImmunologyT follicular helper cellsapoptotic cellsautoimmune diseasegerminal centerAttribution-NonCommercial-NoDerivatives 4.0 International40252220CELL REPORTSopen access