Induction of autoantibody-mediated spontaneous arthritis critically depends on follicular dendritic cells.
Follicular dendritic cells (FDCs) are important for the induction of protective T cell-dependent humoral responses, but their contribution to autoimmunity remains elusive. Here, gene-targeted interruption of FDC development was combined with the K/BxN mouse model of arthritis. We found that FDCs were essential for autoantibody production through two distinct but cooperative functions. In a T cell-independent fashion, FDCs loaded with autoantigen-containing immune complexes supported germinal center (GC) B cell development. Additionally, the integrity of FDC networks was required for the recruitment of arthritogenic follicular helper T cells, a process that drove T-B cell interactions and productive GC reactivity. Importantly, pharmacological interference in the maintenance of FDCs ameliorated disease development, suggesting the FDC as a potential target for dampening autoimmunity.
Victoratos
Panayiotis
P
Institute of Immunology, Biomedical Sciences Research Center Alexander Fleming, Vari, Attica, Greece. p.victoratos@fleming.gr
Kollias
George
G
D000818:Animals; D001168:Arthritis / Q000276:immunology*; D001323:Autoantibodies; D001402:B-Lymphocytes / Q000276:immunology*; D020566:Dendritic Cells, Follicular / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology*; D007156:Immunologic Memory; D051379:Mice; D008822:Mice, Transgenic
D001323:Autoantibodies