In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo

Takuya Nojima, Kei Haniuda, Tatsuya Moutai, Moeko Matsudaira, Sho Mizokawa, Ikuo Shiratori, Takachika Azuma and Daisuke Kitamura ()
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Takuya Nojima: Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan.
Kei Haniuda: Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan.
Tatsuya Moutai: Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan.
Moeko Matsudaira: Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan.
Sho Mizokawa: Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan.
Ikuo Shiratori: Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan.
Takachika Azuma: Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan. Correspondence and requests for materials should be addressed to D.K. (email: ).
Daisuke Kitamura: Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan.

Nature Communications, 2011, vol. 2, issue 1, 1-11

Abstract: 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.

Date: 2011
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DOI: 10.1038/ncomms1475

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