Allan Lenka L, Hoefl Katrin, Zheng Dong-Jun, Chung Brian K, Kozak Frederick K, Tan Rusung, van den Elzen Peter
Department of Pathology and Laboratory Medicine, University of British Columbia, Child and Family Research Institute, Vancouver, Canada.
Blood. 2009 Sep 17;114(12):2411-6. doi: 10.1182/blood-2009-04-211417. Epub 2009 Jul 20.
Natural killer T (NKT) cells are innate-like lymphocytes that recognize lipid antigens and have been shown to enhance B-cell activation and antibody production. B cells typically recruit T-cell help by presenting internalized antigens recognized by their surface antigen receptor. Here, we demonstrate a highly efficient means whereby human B cells present lipid antigens to NKT cells, capturing the antigen using apolipoprotein E (apoE) and the low-density lipoprotein receptor (LDL-R). ApoE dramatically enhances B-cell presentation of alpha-galactosylceramide (alphaGalCer), an exogenous CD1d presented antigen, inducing activation of NKT cells and the subsequent activation of B cells. B cells express the LDL-R on activation, and the activation of NKT cells by B cells is completely LDL-R dependent, as shown by blocking experiments and the complete lack of presentation when using apoE2, an isoform of apoE incapable of LDL-R binding. The dependence on apoE and the LDL-R is much more pronounced in B cells than we had previously seen in dendritic cells, which can apparently use alternate pathways of lipid antigen uptake. Thus, B cells use an apolipoprotein-mediated pathway of lipid antigen presentation, which constitutes a form of innate help for B cells by NKT cells.
自然杀伤T（NKT）细胞是一类固有样淋巴细胞，可识别脂质抗原，并已被证明能增强B细胞活化和抗体产生。B细胞通常通过呈递其表面抗原受体识别的内化抗原来募集T细胞辅助。在此，我们展示了一种高效方式，即人类B细胞将脂质抗原呈递给NKT细胞，利用载脂蛋白E（apoE）和低密度脂蛋白受体（LDL-R）捕获抗原。ApoE显著增强B细胞对α-半乳糖神经酰胺（αGalCer，一种外源性CD1d呈递抗原）的呈递，诱导NKT细胞活化以及随后的B细胞活化。B细胞在活化时表达LDL-R，B细胞对NKT细胞的活化完全依赖于LDL-R，这通过阻断实验以及使用apoE2（一种无法与LDL-R结合的apoE异构体）时完全缺乏呈递得以证明。B细胞对apoE和LDL-R的依赖性比我们之前在树突状细胞中所见更为明显，树突状细胞显然可以使用脂质抗原摄取的替代途径。因此，B细胞利用一种载脂蛋白介导的脂质抗原呈递途径，这构成了NKT细胞对B细胞的一种固有辅助形式。
