Division of Molecular Biology, Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan.
Nat Commun. 2011 Sep 6;2:465. doi: 10.1038/ncomms1475.
In response to T cell-dependent antigens, B cells proliferate extensively to form germinal centres (GC), and then differentiate into memory B (B(mem)) cells or long-lived plasma cells (LLPCs) by largely unknown mechanisms. Here we show a new culture system in which mouse naïve B cells undergo massive expansion and isotype switching, and generate GC-phenotype B (iGB) cells. The iGB cells expressing IgG1 or IgM/D, but not IgE, differentiate into B(mem) cells in vivo after adoptive transfer and can elicit rapid immune responses with the help of cognate T cells. Secondary culture with IL-21 maintains the proliferation of the iGB cells, while shifting their in vivo developmental fate from B(mem) cells to LLPCs, an outcome that can be reversed by withdrawal of IL-21 in tertiary cultures. Thus, this system enables in vitro manipulation of B-cell fate, into either B(mem) cells or LLPCs, and will facilitate dissection of GC-B cell differentiation programs.
针对 T 细胞依赖性抗原，B 细胞广泛增殖形成生发中心（GC），然后通过很大程度上未知的机制分化为记忆 B（B(mem)）细胞或长寿浆细胞（LLPC）。在这里，我们展示了一种新的培养系统，其中小鼠幼稚 B 细胞经历大量扩增和同种型转换，并产生生发中心表型 B（iGB）细胞。iGB 细胞表达 IgG1 或 IgM/D，但不表达 IgE，在体内过继转移后分化为 B(mem)细胞，并在同源 T 细胞的帮助下引发快速免疫反应。用 IL-21 进行二次培养维持 iGB 细胞的增殖，同时将其体内发育命运从 B(mem)细胞转变为 LLPC，这一结果可以通过在三级培养中撤回 IL-21 来逆转。因此，该系统能够在体外操纵 B 细胞命运，使其成为 B(mem)细胞或 LLPC，并且将有助于剖析 GC-B 细胞分化程序。
