Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, 95616 CA, USA.
J Autoimmun. 2012 Dec;39(4):315-22. doi: 10.1016/j.jaut.2012.04.004. Epub 2012 Jun 12.
C-type lectin receptors are pattern recognition receptors that are critical for autoimmunity and the immune response. Mincle is a C-type lectin receptor expressed by a variety of antigen presenting cells including macrophages, neutrophils, dendritic cells and B cells; a variety of stimuli including stress are known to induce the expression of Mincle. Mincle is an FcRγ-associated activation receptor that senses damaged cells and upon ligation induces activated macrophages to produce inflammatory cytokines. Recently, while several studies have reported that Mincle plays an important role in macrophage responses to fungal infection its function on B cells remains to be defined. In efforts to elucidate the function of Mincle expressed by B cells, we studied the expression of Mincle on subsets of B cells and analyzed cytokines and synthesized immunoglobulin upon ligation of Mincle. The expression of Mincle on CD27-CD19(+) naïve B cells is significantly higher than CD27 + CD19(+) memory B cells. The stimulation of TLR9 ligand induced Mincle expression on B cells. Furthermore, co-stimulation of TLR9 and Mincle ligand reduced IgG and IgA production from B cells without a significant change in the inflammatory cytokines TNF-α, IL-6, IL-8 and IL-10. Our data identifies Mincle as a potentially critical player in human B cell responses.
C 型凝集素受体是模式识别受体，对于自身免疫和免疫反应至关重要。Mincle 是一种 C 型凝集素受体，表达于多种抗原呈递细胞，包括巨噬细胞、中性粒细胞、树突状细胞和 B 细胞；多种刺激物，包括应激，已知可诱导 Mincle 的表达。Mincle 是一种与 FcRγ 相关的激活受体，可识别受损细胞，在配体结合后诱导激活的巨噬细胞产生炎症细胞因子。最近，虽然有几项研究报告称 Mincle 在巨噬细胞对真菌感染的反应中发挥重要作用，但它在 B 细胞上的功能仍有待确定。为了阐明 B 细胞表达的 Mincle 的功能，我们研究了 Mincle 在 B 细胞亚群上的表达，并分析了 Mincle 配体结合后细胞因子的产生和免疫球蛋白的合成。CD27-CD19(+)幼稚 B 细胞上的 Mincle 表达明显高于 CD27+CD19(+)记忆 B 细胞。TLR9 配体的刺激诱导 B 细胞上的 Mincle 表达。此外，TLR9 和 Mincle 配体的共刺激减少了 B 细胞中 IgG 和 IgA 的产生，而 TNF-α、IL-6、IL-8 和 IL-10 等炎症细胞因子没有明显变化。我们的数据表明 Mincle 是人类 B 细胞反应中的一个潜在关键参与者。
