CD5+ B cells from individuals with systemic lupus erythematosus express granzyme B.

Abstract

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.

DOI: 10.1002/eji.200940113
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@article{Hagn2010CD5BC, title={CD5+ B cells from individuals with systemic lupus erythematosus express granzyme B.}, author={Magdalena Hagn and Verena Ebel and Kai Sontheimer and Elisabeth Schwesinger and Oleg Lunov and Thamara Beyer and Dorit Fabricius and Thomas F E Barth and Andreas Viardot and Stephan Stilgenbauer and Julia Hepp and Karin Scharffetter-Kochanek and Thomas Simmet and Bernd Jahrsd{\"{o}rfer}, journal={European journal of immunology}, year={2010}, volume={40 7}, pages={2060-9} }