Single-cell atlas reveals a high selection of IgA1- or IgG1-expressing plasma cells in patients with psoriasis

Abstract

Psoriasis has been considered as a T-cell driven common inflammatory skin disease. However, thus far, the pathogenetic role of B cells in psoriasis have largely been neglected. To explore the effect of psoriasis on B-cell mediated humoral immune response, we combined single-cell RNA-sequencing (scRNA-seq) and single-cell antigen receptor lineage (BCR)-sequencing (scBCR-seq) analysis to characterize human PBMC (Peripheral blood mononuclear cells). Merged PBMC from three healthy donors and three patients with psoriasis revealed 27 major cellular clusters in the UMAP plots. Interestingly, we found that follicular helper T cells (TFH) and plasma cells (PCs) obviously increased in patients with psoriasis. Further, we demonstrated that BCL6-expressing TFH cells and their helping B cell-derived IGHA1- or IGHG1-expressing PCs, were increased in patients with psoriasis. By analyzing scBCR-seq data, we found that BCR had a low diversity of IGHA and IGHG but not IGHM and IGHD in patients with psoriasis. In line with a low diversity, IGHA and IGHG frequently used IGHV3 in patients with psoriasis. In addition, we found that CDR silent mutations in IGHA and CDR replacement mutations in IGHG increased from patients with psoriasis. Finally, we showed that patients with psoriasis had high BCR selection pressure in CDR and framework regions (FWR) on IGHG and IGHA but not IGHM and IGHD. Altogether, our results suggest that patients with psoriasis had high BCR selection pressure, partly from helping of BCL6-expressing TFH cells, may result in increased IGHG1- or IGHA1-expressing PCs. Further exploration of high BCR selection pressure will provide valuable clues for the treatment of psoriasis.

Keywords: Antibody; B cells; Plasma cells; Psoriasis; Single-cell atlas; TFH cells.