Molecular analyses of B-cell memory development through synthetic immunology

免疫后，B细胞在淋巴器官中增殖形成生发中心(GC)，并分化为长寿血浆(LP)或记忆B(Bmem)细胞。Bmem细胞发育的机制仍然知之甚少，部分原因是缺乏体外模型系统。最近，我们建立了一种培养体系，在这个体系中，幼稚的B细胞经历了大规模的扩增和同型转换，并产生了被称为IGB细胞的GC样B细胞。小鼠IL-4原代培养后的IGB细胞分化为有功能的Bmem样细胞，而IL-21二次培养后的IGB细胞分化为LP细胞，但不分化为IMB细胞。因此，该系统将有助于GC-B细胞分化程序的剖析。结合基因敲除小鼠，我们证明了转录因子Bach2和其他不仅是Bmem发育所必需的。这些因子在IGB细胞中的系统重组将使我们能够理解Bmem的发展机制。

Upon immunization, B cells proliferate to form germinal centers (GC) in the lymphoid organs and differentiate into either long-lived plasma (LP) or memory B (Bmem) cells. Mechanisms for Bmem cell development remain poorly understood, partly due to the lack of an in vitro model system. Recently, we have established a culture system in which naïve B cells undergo massive expansion and isotype switching, and generate GC-like B cells termed iGB cells. The iGB cells after primary IL-4 culture differentiate into functional Bmem-like (iMB) cells in mice, whereas those after the secondary IL-21 culture differentiate into LP but not iMB cells. Thus, this system will facilitate dissection of GC-B cell differentiation programs. In conjunction with knock-out mice, we demonstrated that transcription factor Bach2 and others are required not only for Bmem development. Systematic reconstitution of these factors in iGB cells will allow us to understand the mechanism for Bmem development.