β-Defensin production by human colonic plasma cells: A new look at plasma cells in ulcerative colitis

Abstract

Previously, we showed that colonic epithelium of ulcerative colitis (UC) patients expresses increased levels of mRNA for 3 antimicrobial peptides, human beta-defensin 2 (hBD-2), hBD-3, and hBD-4 compared to controls. Human colon mucosa was analyzed using double immunofluorescence staining, in situ hybridization, immunoelectron microscopy, and quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) with specific antibodies and probes in the respective assays. We demonstrate that lamina propria in colon from UC patients, Crohn's colitis patients, and controls contain cells that express hBD-2. These cells were identified as mature plasma cells by the highly specific CD138 marker, by their prominent IgA or IgG expression, and by their ultrastructural characteristics. By immunoelectron microscopy it was furthermore shown that the hBD-2 peptide was expressed in rough endoplasmic reticulum, the Golgi complex, and cytoplasmic vesicles, reflecting consecutive steps of synthesis and transport for secretion. Plasma cells were 2-3 times more abundant in UC colon than in control colon and Crohn's colitis. Moreover, plasma cells in UC colon expressed hBD-3 and hBD-4 mRNA. Additionally, hBD-2 mRNA expression was demonstrated in 3 out of 4 well-characterized plasma cell lines. Mature colonic plasma cells can express multiple beta-defensins. In UC, defensin production by plasma cells is probably clinically relevant since plasma cells accumulate in large numbers between the distorted crypts and muscularis mucosae, first focally than diffusely, so as to protect against microbial attack.