title: In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo.
abstract: 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.
authors: Division of Molecular Biology, Research Institute for Biological Sciences (RIBS), Tokyo University of Science, Noda, Chiba 278-0022, Japan. kitamura@rs.noda.tus.ac.jp
authors: Takuya
authors: T
authors: Nojima
authors: Kei
authors: K
authors: Haniuda
authors: Tatsuya
authors: T
authors: Moutai
authors: Moeko
authors: M
authors: Matsudaira
authors: Sho
authors: S
authors: Mizokawa
authors: Ikuo
authors: I
authors: Shiratori
authors: Takachika
authors: T
authors: Azuma
authors: Daisuke
authors: D
authors: Kitamura
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D005434:Flow Cytometry; D007156:Immunologic Memory; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000502:physiology; D007378:Interleukins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D000941:Antigens; D007378:Interleukins; D015847:Interleukin-4; D000098546:Interleukin-21