Dufaud Chad R, McHeyzer-Williams Louise J, McHeyzer-Williams Michael G
Department of Immunology and Microbial Sciences, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States.
Department of Immunology and Microbial Sciences, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States.
Curr Opin Immunol. 2017 Apr;45:112-118. doi: 10.1016/j.coi.2017.03.007. Epub 2017 Mar 17.
Successful vaccination relies on driving the immune response towards high specificity, affinity and longevity. Germinal centers facilitate the evolution of antigen-specific B cells by iterative rounds of diversification, selection, and differentiation to memory and plasma cells. Experimental evidence points to B cell receptor affinity and amount of antigen presented to follicular helper T cells as main drivers of clonal evolution. Concurrent studies suggest that modifiers of cognate contact, temporal mechanisms, and stochastic factors can also shape diversity and influence differentiation to memory and plasma cells, but molecular pathways driving these selection decisions are unresolved. Due to rapid cycles of transcriptional change in the germinal center, single-cell resolution is imperative to dissect mechanisms dictating the mature antigen-specific repertoire. Future studies linking high-resolution analysis of this diverse evolving population with cellular outcome are needed to fully understand the complex mechanisms of selection driving antigen-specific humoral immunity.
成功的疫苗接种依赖于促使免疫反应具有高特异性、高亲和力和长效性。生发中心通过多样化、选择以及分化为记忆细胞和浆细胞的迭代轮次，促进抗原特异性B细胞的进化。实验证据表明，B细胞受体亲和力以及呈递给滤泡辅助性T细胞的抗原量是克隆进化的主要驱动因素。同时进行的研究表明，同源接触的调节因子、时间机制和随机因素也可以塑造多样性并影响向记忆细胞和浆细胞的分化，但驱动这些选择决定的分子途径尚未明确。由于生发中心转录变化的快速循环，单细胞分辨率对于剖析决定成熟抗原特异性库的机制至关重要。未来需要将对这个多样化不断进化群体的高分辨率分析与细胞结果联系起来的研究，以充分理解驱动抗原特异性体液免疫的复杂选择机制。
