PD-1:PD-1 ligand interactions suppress B-1b cell responses to T cell-independent type 2 antigens (61.7)

Abstract

Abstract B-1b cells play a key role in producing antibodies (Ab) in response to T cell-independent type 2 (TI-2) antigens (Ags). However, the factors regulating Ab production by this unique B cell subset are not well understood. In this study, the role of the PD-1 immunoinhibitory receptor in regulating B-1b cell responses to TI-2 Ags was investigated in normal mice. Following TNP-Ficoll immunization, Ag-specific B-1b cells transiently expressed PD-1, which suppresses BCR-induced B-1b cell proliferation when ligated in vitro. In vivo administration of an Ab that blocks PD-1 from interacting with its ligands during the first 3 days following TNP-Ficoll immunization significantly enhanced Ag-specific B-1b cell expansion and differentiation relative to mice that had received control Ab. Serum levels of Ag-specific IgG3, the major IgG isotype produced in response to TI-2 Ags, remained significantly elevated in PD-1 mAb-treated mice for at least 6 weeks post-immunization. Remarkably, PD-1 mAb administration during the first few days following immunization resulted in significantly increased numbers of both splenic and bone marrow Ag-specific IgG3, but not IgM, secreting cells at both early (day 5) and late (6 week) timepoints. Thus, PD-1:PDL interactions occurring shortly after initial TI-2 Ag encounter play a critical role in suppressing Ag-specific B-1b cell expansion and the development of long-term IgG3-producing bone marrow and spleen cells.