B cells play a major role in the adaptive immune response by producing antigen-specific antibodies against pathogens and imparting immunological memory. Following infection or vaccination, antibody-secreting B cells and memory B cells are generated in specialized regions of lymph nodes and spleens, called germinal centers. Here, we report a fully synthetic ex-vivo system that recapitulates the generation of antigen-specific germinal-center (GC) like B cells using material-surface driven polyvalent signaling. This synthetic germinal center (sGC) reaction was effectively induced using biomaterial-based artificial “follicular T helper cells (T_FH)” that provided both natural CD40⁻CD40L ligation as well as crosslinking of CD40; and by mimicking artificial “follicular dendritic cells (FDC)” to provide efficient, polyvalent antigen presentation. The artificial sGC reaction resulted in efficient B cell expansion, immunoglobulin (Ig) class switching, and expression of germinal center phenotypes. Antigen presentation during sGC reaction selectively enhanced the antigen-specific B cell population and induced somatic hyper-mutations for potential affinity maturation. The resulting B cell population consisted primarily of GC-like B cells (centrocytes) as well as some plasma-like B cells expressing CD138. With concurrent cell sorting, we successfully created highly enriched populations of antigen-specific B cells. Adoptive transfer of these GC-like B cells into non-irradiated isogeneic or non-lethally irradiated congenic recipient mice showed successful engraftment and survival of the donor cells for the 4 week test period. We show that this material-surface driven sGC reaction can be successfully applied to not only splenic B cells but also B cells isolated from more therapeutically relevant sources such as peripheral blood mononuclear cells (PBMCs), thus making our current work an exciting prospect in the new era of personalized medicine and custom-immunotherapy.

B细胞通过产生针对病原体的抗原特异性抗体并赋予免疫记忆，在适应性免疫应答中起主要作用。感染或接种疫苗后，会在称为生发中心的淋巴结和脾脏的特殊区域中产生分泌抗体的B细胞和记忆B细胞。在这里，我们报告了一个完全合成的离体系统，该系统使用材料表面驱动的多价信号传导概括了抗原特异性生发中心（GC）像B细胞的生成。使用基于生物材料-人工“滤泡辅助性T细胞（T这种合成生发中心（SGC）反应物有效地诱导_FH所提供天然CD40）” ^-CD40L连接以及CD40交联；并通过模仿人工“滤泡树突状细胞（FDC）”来提供有效的多价抗原提呈。人工sGC反应导致有效的B细胞扩增，免疫球蛋白（Ig）类转换和生发中心表型的表达。sGC反应过程中的抗原呈递选择性地增强了抗原特异性B细胞的数量，并诱导了体细胞超突变，以促进潜在的亲和力成熟。所得的B细胞群体主要由GC样B细胞（中心细胞）以及一些表达CD138的血浆样B细胞组成。通过同时进行细胞分选，我们成功地创建了高度富集的抗原特异性B细胞群体。这些GC样B细胞过继转移到未辐照的同基因或非致命地辐照的同基因受体小鼠中，表明供体细胞成功植入并存活了4周。我们表明，这种由材料表面驱动的sGC反应不仅可以成功地应用于脾脏B细胞，而且还可以成功地从较治疗相关的来源（例如外周血单核细胞（PBMC））分离的B细胞应用，从而使我们目前的工作在人类中具有令人兴奋的前景。个性化医学和定制免疫疗法的新时代。