CD5+ B cells from individuals with systemic lupus erythematosus express granzyme B
CD5+ B cells from individuals with systemic lupus erythematosus express granzyme B
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DOI：
10.1002/eji.200940113
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发表时间：
2010-07-01
影响因子：
5.4
通讯作者：
Jahrsdoerfer, Bernd
中科院分区：
文献类型：
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作者：
Hagn, Magdalena;Ebel, Verena;Jahrsdoerfer, Bernd
最近，我们报道了IL-21诱导慢性淋巴细胞白血病患者的恶性CD 5（+）B细胞的颗粒酶B（Gzm B）和Gzm B依赖性凋亡。几种自身免疫性疾病（AD）与CD 5（+）B细胞频率增加有关。由于AD也与IL-21和Gzm B水平升高有关，我们推测CD 5（+）B细胞、IL-21和Gzm B之间存在联系。在此，我们证实了系统性红斑狼疮（SLE）患者血清中IL-21和Gzm B水平高度相关，并且新鲜分离的CD 5（+）SLE B细胞组成性表达Gzm B。IL-21在体外直接诱导几种AD和脐带血的CD 5（+）B细胞表达和分泌Gzm B，同时存在BCR刺激强烈增强了这一过程。此外，IL-21抑制SLE个体的CD 5（+）B细胞的活力和扩增。总之，我们的研究可以解释SLE和其他AD患者IL-21和GzmB水平升高的原因。此外，我们的数据表明，IL-21可能通过诱导CD 5（+）B细胞中的Gzm B并抑制其扩增而具有疾病修饰特征。我们的研究结果为进一步评价IL-21在某些AD如SLE中的治疗潜力提供了理论基础。
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.