CD5+ B cells from individuals with systemic lupus erythematosus express granzyme B.
Recently, we reported that IL-21 induces granzyme B (GzmB) and GzmB-dependent apoptosis in malignant CD5(+) B cells from patients with chronic lymphocytic leukemia. Several autoimmune diseases (AD) are associated with enhanced frequencies of CD5(+) B cells. Since AD are also associated with elevated IL-21 and GzmB levels, we postulated a link between CD5(+) B cells, IL-21 and GzmB. Here, we demonstrate that IL-21 and GzmB serum levels are highly correlated in subjects with systemic lupus erythematosus (SLE) and that freshly isolated CD5(+) SLE B cells constitutively express GzmB. IL-21 directly induced GzmB expression and secretion by CD5(+) B cells from several AD and from cord blood in vitro, and the simultaneous presence of BCR stimulation strongly enhanced this process. Furthermore, IL-21 suppressed both viability and expansion of CD5(+) B cells from SLE individuals. In summary, our study may explain the elevated levels of IL-21 and GzmB in SLE and other AD. Moreover, our data suggest that IL-21 may have disease-modifying characteristics by inducing GzmB in CD5(+) B cells and by suppressing their expansion. Our results provide the rationale for further evaluation of the therapeutic potential of IL-21 in certain AD such as SLE.
Hagn
Magdalena
M
Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University, Ulm, Germany.
Ebel
Verena
V
Sontheimer
Kai
K
Schwesinger
Elisabeth
E
Lunov
Oleg
O
Beyer
Thamara
T
Fabricius
Dorit
D
Barth
Thomas F E
TF
Viardot
Andreas
A
Stilgenbauer
Stephan
S
Hepp
Julia
J
Scharffetter-Kochanek
Karin
K
Simmet
Thomas
T
Jahrsdörfer
Bernd
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018956:CD5 Antigens / Q000096:biosynthesis; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D005260:Female; D053804:Granzymes / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance; D007378:Interleukins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020239:Receptor Cross-Talk / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D053655:Receptors, Interleukin-21 / Q000096:biosynthesis / Q000235:genetics; D000098546:Interleukin-21
D018956:CD5 Antigens; D007378:Interleukins; D011947:Receptors, Antigen, B-Cell; D053655:Receptors, Interleukin-21; D053804:Granzymes; D000098546:Interleukin-21