Tolerance without clonal expansion: self-antigen-expressing B cells program self-reactive T cells for future deletion.
B cells have been shown in various animal models to induce immunological tolerance leading to reduced immune responses and protection from autoimmunity. We show that interaction of B cells with naive T cells results in T cell triggering accompanied by the expression of negative costimulatory molecules such as PD-1, CTLA-4, B and T lymphocyte attenuator, and CD5. Following interaction with B cells, T cells were not induced to proliferate, in a process that was dependent on their expression of PD-1 and CTLA-4, but not CD5. In contrast, the T cells became sensitive to Ag-induced cell death. Our results demonstrate that B cells participate in the homeostasis of the immune system by ablation of conventional self-reactive T cells.
Frommer
Friederike
F
I. Medical Department, Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 63, Mainz, Germany.
Heinen
Tobias J A J
TJ
Wunderlich
F Thomas
FT
Yogev
Nir
N
Buch
Thorsten
T
Roers
Axel
A
Bettelli
Estelle
E
Müller
Werner
W
Anderton
Stephen M
SM
Waisman
Ari
A
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D001324:Autoantigens / Q000096:biosynthesis / Q000276:immunology*; D015551:Autoimmunity / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018956:CD5 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D060908:CTLA-4 Antigen; D049109:Cell Proliferation; D017637:Clonal Deletion / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D061026:Programmed Cell Death 1 Receptor; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D001324:Autoantigens; D018956:CD5 Antigens; D060908:CTLA-4 Antigen; C526836:Cd5 protein, mouse; C556707:Ctla4 protein, mouse; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor