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

Nat Commun. 2011 Sep 6;2:465. doi: 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 (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Antigens / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Proliferation
  • Flow Cytometry
  • Immunologic Memory*
  • In Vitro Techniques
  • Interleukin-4 / physiology
  • Interleukins / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Plasma Cells / cytology
  • Plasma Cells / immunology*

Substances

  • Antigens
  • Interleukins
  • Interleukin-4
  • interleukin-21