A feeder-free differentiation system identifies autonomously proliferating B cell precursors in human bone marrow
Authors
- 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
- Journal of Immunology
Citation
- J Immunol 192 (3): 1044-1054
Abstract
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.