期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 40, 期 7, 页码 2060-2069出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.200940113
关键词
Apoptosis; Autoimmunity; B cells; BCR; Immune regulation
类别
资金
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [JA 1769/1-1]
- Deutsche Jose Carreras Leukamiestiftung [SP 07/10]
- Deutscher Akademischer Austauschdienst (DAAD, German Academic Exchange Service) [D/08/11870]
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.
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