PD-1 expressing B cells are expanded in lupus 4452

Description Lupus is a complex autoimmune disease that involves dysregulation of the B cell compartment. Potential mechanisms for this dysregulation include abnormalities in immune dampening pathways, such as the programmed cell death 1 receptor (PD-1). Though PD-1 functions as a negative regulator in T cells, its role in B cells is not clear. We used comprehensive flow and mass cytometry to examine the expression of PD-1 on peripheral blood B cells from lupus and healthy controls in two large patient cohorts. PD-1 was increased on antigen experienced B cells including double negative, memory, and CD11c+ age-associated B cells. Heterogeneity in patient PD-1+ B cells was uncovered, including an enriched PD-1+CD11c+CXCR3+ B cell subset which we speculate may be pathogenic due to their potential to migrate to sites of inflammation, and a diminished PD-1+PD-L1+ B cell subset which we expect is an immunosuppressive phenotype. PD-1 expression was higher in patients with elevated anti-dsDNA, high disease activity and increased with in vitro stimulation (anti-BCR and TLR9). Surprisingly, PD-1+ B cells proliferated more than PD-1- B cells, and PD-1 blockade with an anti-PD-1 antibody further increased proliferation. Our results suggest that PD-1 function in B cells is different than its inhibitory signaling role in T cells. Further, the expansion of PD-1 expressing B cells in lupus, especially in patients with high disease activity, highlights a new potential pathogenic B cell population.