Monovalent ligation of the B cell receptor induces receptor activation but fails to promote antigen presentation
Monovalent ligation of the B cell receptor induces receptor activation but fails to promote antigen presentation
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DOI：
10.1073/pnas.0511315103
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发表时间：
2006-02-28
影响因子：
11.1
通讯作者：
Ploegh, HL
中科院分区：
文献类型：
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作者：
Kim, YM;Pan, JYJ;Ploegh, HL
我们探讨了抗原价在B细胞受体（BCR）激活和细胞内MHC 11类区室重排中的作用，这些因素有助于抗原呈递的功效。使用表达鸡蛋溶菌酶（HEL）特异性BCR的原代B细胞，我们发现寡聚HEL比单价HEL更有效地促进BCR活化和内化，尽管单价HEL与抗Ig的单价Fab B片段不同，容易触发BCR。尽管如此，寡价连接将BCR定位在膜微结构域中，该膜微结构域不同于单价连接过程中参与的膜微结构域，如通过BCR的去污剂提取所判断的。此外，寡价HEL诱导更显着的重组MHC II类抗原加工区室。使用视频显微镜，我们在真实的时间观察MHC 11类区室的重排以及抗原在原代6细胞中的递送。观察到的MHC II类阳性区室重排的增加和其中抗原结合的BCR的处置与改善的HEL-clerived表位的呈递相关。尽管单体HEL有效地接合BCR，但与寡价抗原相比，HEL衍生的表位的呈递受损。这种特性可能有助于解释已知的可溶性、解聚抗原诱导B细胞耐受状态的能力。
We explored the role of antigen valency in B cell receptor (BCR) activation and rearrangement of intracellular MHC class 11 compartments as factors that contribute to the efficacy of antigen presentation. Using primary B cells that express a hen egg lysozyme (HEL)-specific BCR, we found that oligomeric HEL more efficiently promoted both BCR activation and internalization than did monovalent HEL, although monovalent HEL, unlike monovalent Fab fragments of anti-Ig, readily triggered the BCR. Nonetheless, oligovalent ligation positions the BCR in a membrane microdomain that is distinct from one engaged in the course of monovalent ligation, as judged by detergent extraction of the BCR. Furthermore, oligovalent HEL induced more pronounced rearrangement of MHC class II-containing antigen-processing compartments. Using videomicroscopy we observed in real time the rearrangement of MHC class 11 compartments as well as delivery of antigen in primary 6 cells. The observed increase in rearrangement of MHC class II-positive compartments and the disposition of antigen-bound BCRs therein correlates with improved presentation of a HEL-clerived epitope. Although monomeric HEL efficiently engages the BCR, presentation of HEL-derived epitopes is impaired compared to oligovalent antigens. This trait may help explain the known ability of soluble, disaggregated antigen to induce a state of B cell tolerance.