Cutting Edge: Active TGF-β1 Released from GARP/TGF-β1 Complexes on the Surface of Stimulated Human B Lymphocytes Increases Class-Switch Recombination and Production of IgA

Production of active TGF-beta is regulated at a posttranslational level and implies release of the mature cytokine dimer from the inactive, latent TGF-beta precursor. There are several cell-type specific mechanisms of TGF-beta activation. We identified a new mechanism operating on the surface of human regulatory T cells and involving membrane protein GARP, which binds latent TGF-beta 1. The paracrine activity of regulatory T cell-derived TGF-beta 1 contributes to immunosuppression and can be inhibited with anti-GARP Abs. Whether other immune cell types use surface GARP to activate latent TGF-beta 1 was not known. We show in this study that stimulated, human B lymphocytes produce active TGF-beta 1 from surface GARP/latent TGF-beta 1 complexes with isotype switching to IgA production.