title: Increased IL-21 Expression Induces Granzyme B in Peripheral CD5(+) B Cells as a Potential Counter-Regulatory Effect in Primary Sjögren's Syndrome.
abstract: Recently, we reported elevated proportions of circulating follicular T helper cells and higher levels of interleukin- (IL-) 21 in primary Sjögren's syndrome (pSS). Interaction of invariant natural killer T (iNKT) cells with B cells and granzyme B (GrB) production may be also important in pSS. Thirty-two pSS patients and 24 healthy controls were enrolled in our study. We investigated the expression of intracellular GrB and IL-21 receptor (IL-21R) of CD19(+)CD5(+) and CD19(+)CD5(-) B cells; furthermore, we determined the IL-21 expression of iNKT cells as well. We also assessed the proportion of transitional (CD19(+)CD24(high)CD38(high)), mature (CD19(+)CD24(int)CD38(int)) and primarily memory (CD19(+)CD24(high)CD38(-)) B cells. CD5(+) but not CD5(-) B cells showed elevated GrB and IL-21R expression in pSS; additionally IL-21 expression of iNKT cells was also elevated. The ratios of transitional and mature B cells were elevated in pSS, while primarily memory B cell percentages were decreased, which correlated with GrB and IL-21R expression of CD19(+) B cells. Our results suggest that enhanced IL-21R expression of CD19(+)CD5(+) B cells and production of IL-21 by iNKT cells may play an important role in the pathogenesis of pSS by regulating CD19(+)CD5(+) B cell functions and increasing GrB production, presumably leading to a counter-regulatory effect in the disease.
authors.affiliation: Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Móricz Zsigmond Street 22, Debrecen 4032, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Papp
authors.affiliation: Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Móricz Zsigmond Street 22, Debrecen 4032, Hungary.
authors.forename: Edit
authors.initials: E
authors.lastname: Gyimesi
authors.affiliation: Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Móricz Zsigmond Street 22, Debrecen 4032, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Szabó
authors.affiliation: Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Móricz Zsigmond Street 22, Debrecen 4032, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Zöld
authors.affiliation: Division of Clinical Immunology, Faculty of Medicine, University of Debrecen, Móricz Zsigmond Street 22, Debrecen 4032, Hungary.
authors.forename: Margit
authors.initials: M
authors.lastname: Zeher
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism*; D018956:CD5 Antigens / Q000378:metabolism*; D005260:Female; D053804:Granzymes / Q000378:metabolism*; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053655:Receptors, Interleukin-21 / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000378:metabolism*; D000098546:Interleukin-21
chemical_list: D018941:Antigens, CD19; D018956:CD5 Antigens; D007378:Interleukins; D053655:Receptors, Interleukin-21; D051997:ADP-ribosyl Cyclase 1; C509213:GZMB protein, human; D053804:Granzymes; D000098546:Interleukin-21