Plasma cells in the mucosa of patients with inflammatory bowel disease produce granzyme B and possess cytotoxic activities.
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.
Department of Systems Medicine, University of Rome "Tor Vergata," 00133 Rome, Italy;
Maria Laura
ML
Cupi
Department of Systems Medicine, University of Rome "Tor Vergata," 00133 Rome, Italy;
Massimiliano
M
Sarra
Department of Systems Medicine, University of Rome "Tor Vergata," 00133 Rome, Italy;
Irene
I
Marafini
Department of Systems Medicine, University of Rome "Tor Vergata," 00133 Rome, Italy;
Ivan
I
Monteleone
Department of Systems Medicine, University of Rome "Tor Vergata," 00133 Rome, Italy;
Eleonora
E
Franzè
Department of Systems Medicine, University of Rome "Tor Vergata," 00133 Rome, Italy;
Angela
A
Ortenzi
Department of Systems Medicine, University of Rome "Tor Vergata," 00133 Rome, Italy;
Alfredo
A
Colantoni
Department of Surgery, University of Rome "Tor Vergata," 00133 Rome, Italy;
Giuseppe
G
Sica
Department of Surgery, University of Rome "Tor Vergata," 00133 Rome, Italy;
Pierpaolo
P
Sileri
Immunology Area, Research Center, Bambino Gesù Children's Hospital, 00165 Rome, Italy; and.
M Manuela
MM
Rosado
Immunology Area, Research Center, Bambino Gesù Children's Hospital, 00165 Rome, Italy; and.
Rita
R
Carsetti
Barts and the London School of Medicine and Dentistry, London E1 2AD, United Kingdom.
Thomas T
TT
MacDonald
Department of Systems Medicine, University of Rome "Tor Vergata," 00133 Rome, Italy;
Francesco
F
Pallone
Department of Systems Medicine, University of Rome "Tor Vergata," 00133 Rome, Italy; Gi.Monteleone@Med.uniroma2.it.
Giovanni
G
Monteleone
D018941:Antigens, CD19 / Q000276:immunology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology*; D053804:Granzymes / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D008297:Male; D010950:Plasma Cells / Q000276:immunology* / Q000473:pathology
D018941:Antigens, CD19; D007070:Immunoglobulin A; C509213:GZMB protein, human; D053804:Granzymes