A role for PD1-PDL1/2 regulatory axis in suppressing T cell independent memory B cell generation and activation.

Abstract

Abstract T cell-independent type 2 antigens (TI-2 Ags), including polysaccharides present on the surface of encapsulated bacteria, are limited in their capacity to generate a recall response. The failure of native polysaccharide-based vaccine-elicited antibody responses to boost following either revaccination or natural infection is a barrier to establishing protection against infectious diseases and is a poorly understood facet of humoral immunity. Previous work has indicated a role for antigen-specific IgG in suppressing TI-2 antibody recall responses, but questions remain as to how TI-2 memory B cell formation and reactivation is regulated. In the current study, we investigated the role of the PD1-PDL regulatory axis in regulating B cell recall responses to TI-2 Ags. Using adoptive transfers of B cells from VHB1–8 transgenic mice in which a fraction of B cells express specificity for NP, we demonstrate B cell-intrinsic PD-1 expression suppresses memory B cell (Bmem) generation as well as Bmem reactivation in response to NP-Ficoll. B cell-extrinsic PDL1 and PDL2 both contribute to suppression of Bmem generation and reactivation. B cell-extrinsic PDL1 and Bmem-intrinsic PDL2 expression play key roles in PD-1-mediated suppression of Bmem reactivation and antibody production. In summary, this work highlights a key role for PD-1 and its ligands in regulating the formation and functional reactivation of TI-2 Ag-specific memory B cells and reveals new avenues for improving TI-2 Ag-based vaccine responses.