Transcriptional profiling of human intestinal plasma cells reveals effector functions beyond antibody production

Abstract

Background: Plasma cells (PCs) are terminally differentiated B-lymphocytes producing antibodies. In coeliac disease (CeD) there is increased density of PCs in the small-intestinal lesion. Many of these PCs produce disease-specific autoantibodies targeting transglutaminase 2 (TG2). Objective: The plasmacytosis of CeD motivated us to study the transcriptional programme of PCs from coeliac gut lesions. Methods: RNA-seq was performed on the PCs of CeD patients and disease controls, being specific or non-specific for TG2. Results: Being antibody-producing cells, 67% of the PCs’ transcript was aligned to immunoglobulin genes. Strikingly, genes encoding ligands and receptors of chemokines and cytokines were abundant. Higher transcript levels of genes associated with cell activation and immune responses were observed in PCs of CeD patients compared to controls. TG2-specific compared to non-TG2 specific PCs expressed increased levels of CXCR3, CXCL10 and interleukin-15; factors that have been implicated in the pathogenesis of CeD yet with production attributed to other cells than PCs. The presence of transcripts of HLA class II and T-cell co-stimulatory molecules suggests that PCs may serve as antigen-presenting cells for CD4 + helper T cells. Conclusions: Our findings shed new light on the biology of intestinal PCs, implicating functions that go beyond the production of immunoglobulins.