Lipid Membrane-Based Antigen Presentation to B Cells Using a Fully Synthetic Ex Vivo Germinal Center Model.
Lipid Membrane-Based Antigen Presentation to B Cells Using a Fully Synthetic Ex Vivo Germinal Center Model.
复制标题
使用全合成离体生发中心模型将基于脂膜的抗原呈递至 B 细胞。
DOI：
10.1002/anbr.202100137
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发表时间：
2022
影响因子：
3.4
通讯作者：
Roy,Krishnendu
中科院分区：
文献类型：
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作者：
Kramer,Liana;Song,HannahW;Mitchell,Kaiya;Kartik,Mythili;Jain,Ritika;Escarra,VictoriaLozano;Quiros,Enrique;Fu,Harrison;Singh,Ankur;Roy,Krishnendu
高亲和力抗原特异性B细胞在淋巴器官内的专门结构、生发中心（GC）内产生。在GC中，滤泡树突状细胞（FDC）将其膜表面上的抗原呈递给同源B细胞，诱导B细胞向抗体分泌细胞快速增殖和分化。FDC的流体膜表面允许B细胞将抗原“拉”成簇并内化它们，这一过程通常涉及撕掉和内化FDC膜片段。为了离体研究该过程，使用脂质体膜作为抗原呈递FDC样液体脂质表面以激活B细胞。在完全合成的体外GC模型（sGC）中，该模型使用基于微珠的CD40配体呈递和细胞因子混合物来模拟T滤泡辅助细胞向B细胞的信号，呈递模型抗原模拟物的脂质体有效地结合B细胞受体（BCR），并诱导比可溶性抗原更大的BCR聚集，导致快速抗原内化和B细胞增殖。B细胞显示GC样反应，并进行有效的IgG 1类别转换。总之，结果表明，流体膜结合抗原诱导强烈的GC反应，并提供了一种新的合成体外系统，用于研究健康和疾病中的GC生物学，以及用于体外扩增治疗性B细胞。
High‐affinity antigen‐specific B cells are generated within specialized structures, germinal centers (GCs), inside lymphoid organs. In GCs, follicular dendritic cells (FDCs) present antigens on their membrane surface to cognate B cells, inducing rapid proliferation and differentiation of the B cells toward antibody‐secreting cells. The FDC's fluid membrane surface allows B cells to “pull” the antigens into clusters and internalize them, a process that frequently involves tearing off and internalizing FDC membrane fragments. To study this process ex vivo, liposomal membranes are used as the antigen‐presenting FDC‐like fluid lipid surface to activate B cells. In a fully synthetic in vitro GC model (sGC), which uses the microbead‐based presentation of the CD40 Ligand and a cytokine cocktail to mimic T follicular helper cell signals to B cells, liposomes presenting a model antigen mimic effectively engage B cell receptors (BCRs) and induce greater BCR clustering compared to soluble antigens, resulting in rapid antigen internalization and proliferation of the B cells. B cells showed GC‐like reactions and undergo efficient IgG1 class‐switching. Taken together, the results suggest that fluid membrane‐bound antigen induces a strong GC response and provides a novel synthetic in vitro system for studying GC biology in health and diseases, and for expanding therapeutic B cells ex vivo.