Plasma cells in the mucosa of patients with inflammatory bowel disease produce granzyme B and possess cytotoxic activities.

Abstract

In both Crohn's disease (CD) and ulcerative colitis (UC), the gut is massively infiltrated with B cells and plasma cells, but the role of these cell types in the pathogenesis of gut tissue damage remains largely unknown. Human B cells express granzyme B (GrB) when cultured with IL-21, a cytokine overproduced in CD and UC mucosa. We therefore examined whether mucosal B cells express GrB and have cytotoxic activity in inflammatory bowel disease (IBD). GrB-expressing CD19(+) and IgA(+) cells were seen in the normal intestinal mucosa, but they were significantly more frequent in both CD and UC. In contrast, only a minority of CD19(+) and IgA(+) cells expressed perforin with no difference between IBD and controls. GrB-producing CD19(+) cells expressed CD27 and were CD38(high) and CD20 negative. CD19(+) B cells from IBD patients induced HCT-116 cell death. IL-21 enhanced GrB expression in control CD19(+) B cells and increased their cytotoxic activity. These data indicate that IBD-related inflammation is marked by mucosal accumulation of cytotoxic, GrB-expressing CD19(+) and IgA(+) cells, suggesting a role for these cells in IBD-associated epithelial damage.

• Authors: Maria Laura Cupi, Massimiliano Sarra, Irene Marafini, Ivan Monteleone, Eleonora Franzè, Angela Ortenzi, Alfredo Colantoni, Giuseppe Sica, Pierpaolo Sileri, M Manuela Rosado, Rita Carsetti, Thomas T MacDonald, Francesco Pallone, Giovanni Monteleone
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 192 Issue 12 Pg. 6083-91 (Jun 15 2014) ISSN: 1550-6606 [Electronic] United States
• PMID: 24835396 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 by The American Association of Immunologists, Inc.

Chemical References

• Antigens, CD19
• Immunoglobulin A
• GZMB protein, human
• Granzymes

Topics

• Antigens, CD19 (immunology)
• Female
• Gene Expression Regulation, Enzymologic (immunology)
• Granzymes (immunology)
• Humans
• Immunoglobulin A (immunology)
• Inflammatory Bowel Diseases (immunology, pathology)
• Intestinal Mucosa (immunology, pathology)
• Male
• Plasma Cells (immunology, pathology)