Dominant Role of CD80-CD86 Over CD40 and ICOSL in the Massive Polyclonal B Cell Activation Mediated by LAT(Y136F) CD4(+) T Cells.

Frontiers in Immunology
Stéphane ChevrierHans Acha-Orbea

Abstract

Coordinated interactions between T and B cells are crucial for inducing physiological B cell responses. Mutant mice in which tyrosine 136 of linker for activation of T cell (LAT) is replaced by a phenylalanine (Lat(Y136F)) exhibit a strong CD4(+) T cell proliferation in the absence of intended immunization. The resulting effector T cells produce high amounts of T(H)2 cytokines and are extremely efficient at inducing polyclonal B cell activation. As a consequence, these Lat(Y136F) mutant mice showed massive germinal center formations and hypergammaglobulinemia. Here, we analyzed the involvement of different costimulators and their ligands in such T-B interactions both in vitro and in vivo, using blocking antibodies, knockout mice, and adoptive transfer experiments. Surprisingly, we showed in vitro that although B cell activation required contact with T cells, CD40, and inducible T cell costimulator molecule-ligand (ICOSL) signaling were not necessary for this process. These observations were further confirmed in vivo, where none of these molecules were required for the unfolding of the LAT CD4(+) T cell expansion and the subsequent polyclonal B cell activation, although, the absence of CD40 led to a reduction of the follicular B...Continue Reading

Citations

Aug 20, 2014·Nature Immunology·Bernard MalissenRomain Roncagalli
Feb 9, 2017·Autoimmunity·Phillip P DomeierZiaur S M Rahman
Mar 26, 2013·Nature Reviews. Immunology·Rebecca J Brownlie, Rose Zamoyska
Mar 3, 2020·Frontiers in Immunology·Yosuke KunishitaHideaki Nakajima
Apr 30, 2021·Frontiers in Immunology·Sarah A O'BrienWeiguo Zhang
May 4, 2021·Frontiers in Immunology·Wan-Lin Lo, Arthur Weiss

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Methods Mentioned

BETA
flow cytometry
FACS
FCS
ELISA

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