A feeder-free differentiation system identifies autonomously proliferating B cell precursors in human bone marrow


  • H. Kraus
  • S. Kaiser
  • K. Aumann
  • P. Bönelt
  • U. Salzer
  • D. Vestweber
  • M. Erlacher
  • M. Kunze
  • M. Burger
  • K. Pieper
  • H. Sic
  • A. Rolink
  • H. Eibel
  • M. Rizzi


  • Journal of Immunology


  • J Immunol 192 (3): 1044-1054


  • The peripheral B cell compartment is maintained by homeostatic proliferation and through replenishment by bone marrow precursors. Because hematopoietic stem cells cycle at a slow rate, replenishment must involve replication of precursor B cells. To study proliferation of early human B cell progenitors, we established a feeder cell-free in vitro system allowing the development of B cells from CD34(+) hematopoietic stem cells up to the stage of immature IgM(+) B cells. We found that pro-B and pre-B cells generated in vitro can proliferate autonomously and persist up to 7 wk in culture in the absence of signals induced by exogenously added cytokines. Nevertheless, addition of IL-7 enhanced pre-B cell expansion and inhibited maturation into IgM(+) B cells. The B cell precursor subsets replicating in vitro were highly similar to the bone marrow B cell precursors cycling in vivo. The autonomous proliferation of B cell precursor subsets in vitro and their long-term persistence implies that proliferation during pro-B and pre-B cell stages plays an important role in the homeostasis of the peripheral B cell compartment. Our in vitro culture can be used to study defects in B cell development or in reconstitution of the B cell pool after depletion and chemotherapy.