In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo
In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo
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DOI：
10.1038/ncomms1475
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发表时间：
2011-09-01
影响因子：
16.6
通讯作者：
Kitamura, Daisuke
中科院分区：
文献类型：
--
作者：
Nojima, Takuya;Haniuda, Kei;Kitamura, Daisuke
在T细胞依赖的抗原作用下，B细胞广泛增殖形成生发中心(GC)，然后以未知的机制分化为记忆B细胞(B-mem)或长寿命浆细胞(LLPC)。在这里，我们展示了一种新的培养系统，在该系统中，小鼠幼稚的B细胞经历了大规模的扩增和同型转换，并产生了GC-表型B(IGB)细胞。IGB细胞表达IgG1或IgM/D，但不表达IgE，过继转移后在体内分化为B-mem细胞，并能在同源T细胞的帮助下诱导快速免疫应答。IL-21的二次培养维持了IGB细胞的增殖，同时将其在体内的发育命运从B-mem细胞转移到LLPC，这一结果可以通过第三次培养中IL-21的退出而逆转。因此，该系统能够在体外操纵B细胞的命运，转化为B-mem细胞或LLPC，并将有助于剖析GC-B细胞的分化程序。
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 naive 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.