Document Type
Article
Publication Date
4-14-2026
Original Citation
Funsten M,
de Pooter R,
Varanasi V,
Burrows M,
Block K,
Kuznetsov A,
Serreze DV,
Huang H,
Chervonsky A.
B cells enable autoreactive T cells to avoid suppression. Proc Natl Acad Sci U S A. 2026;123(15):e2536291123.
Keywords
JMG, Animals, B-Lymphocytes, Autoimmunity, T-Lymphocytes, Regulatory, Lymphocyte Activation, Dendritic Cells, Mice, Autoantigens
JAX Source
Proc Natl Acad Sci U S A. 2026;123(15):e2536291123.
ISSN
1091-6490
PMID
41955109
DOI
https://doi.org/10.1073/pnas.2536291123
Grant
D.S. was supported by NIH grant DK95735.
Abstract
Clinical trials and experimental observations have shown that B cells are essential for development of T cell-mediated organ-specific autoimmunity, although their exact contribution is not clear. As antigen presentation by B cells is focused on antigens cognate to their antigen receptors, we reasoned that B cells would facilitate activation of T effector cells (Teff) with the same antigen specificity but would poorly activate regulatory T cells (Treg) due to insufficient presence of antigen-specific Tregs among polyclonal/multispecific Tregs at the early stages of pathogenesis. At the same time, activation of Teff by autoantigens presented by dendritic cells (DC) would be sensitive to by-stander suppression by Tregs as DCs express a variety of antigenic peptides. We used Teff cells (KRN) and B cells (121) reactive to the same antigen - glucose-6-phosphate-isomerase (GPI) to show that KRN T cells activation was sensitive to polyclonal Tregs only when activated by DCs but not by B cells. However, as expected, GPI-specific Tregs were fully capable of suppressing Teff activation by B cells. Our findings shed light on the role of B cells in organ-specific autoimmunity and provide knowledge-based support for application of anti-B cell immunotherapies.
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