In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo
- 6 September 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 2 (1), 465
- https://doi.org/10.1038/ncomms1475
Abstract
In response to T cell-dependent antigens, B cells proliferate extensively to form germinal centres (GC), and then differentiate into memory B (Bmem) 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 Bmem 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 Bmem 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 Bmem cells or LLPCs, and will facilitate dissection of GC-B cell differentiation programs.Keywords
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