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)...

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Published in:Cell reports (Cambridge) Vol. 44; no. 5; p. 115602
Main Authors: He, Chenfei, Wang, Shan, Moreews, Marion, Pei, Shengduo, Chen, Guangchun, Li, Quan-Zhen, Del Monte Monge, Alberto, Ramiro, Almudena R., Cai, Curtis, Gaya, Mauro, Barral, Patricia, Buggert, Marcus, Batista, Facundo D., Karlsson, Mikael C.I.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 27.05.2025
Elsevier
Subjects:
Animals
Antigens, CD1d - immunology
Antigens, CD1d - metabolism
apoptotic cells
Autoantibodies - immunology
autoimmune disease
Autoimmunity
B-Lymphocytes - immunology
CD1d
Cell Differentiation
CP: Immunology
germinal center
Lupus Erythematosus, Systemic - immunology
Lymphocyte Activation - immunology
Mice
Mice, Inbred C57BL
Natural Killer T-Cells - immunology
T follicular helper cells
T Follicular Helper Cells - immunology
T-Lymphocytes, Helper-Inducer - immunology
CP: Immunology
CD1d
germinal center
apoptotic cells
autoimmune disease
T follicular helper cells
ISSN:2211-1247, 2211-1247
Online Access:Get full text
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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. [Display omitted] •Conventional and unconventional T follicular helper cells influence each other•Autoreactive B cell responses are enhanced by the activation of iNKTfh cells•Activation of iNKTfh cells is connected to interaction with CD1d expressed by B cells In this study, He et al. find that there is a balance between conventional and unconventional T helper cells and that this influences autoreactive B cell responses. They find that when iNKTfh cells are activated, they limit the expansion of Tfh cells, but the resulting autoreactive B cell response is increased.
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ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2025.115602