The Journal of Experimental Medicine
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Published online 27 February 2006 doi:10.1084/jem.20052444
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 3, 675-687
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ARTICLE

 Lineage specification and plasticity in CD19– early B cell precursors

Lynn L. Rumfelt, Yan Zhou, Benjamin M. Rowley, Susan A. Shinton, and Richard R. Hardy

Division of Basic Sciences, Fox Chase Cancer Center, Philadelphia, PA 19111

CORRESPONDENCE Richard R. Hardy: rr_hardy{at}fccc.edu

We describe here three CD19– B cell precursor populations in mouse bone marrow identified using 12-color flow cytometry. Cell transfer experiments indicate lineage potentials consistent with multilineage progenitor (MLP), common lymphoid progenitor (CLP), and B lineage–restricted pre-pro–B (Fr. A), respectively. However, single cell in vitro assays reveal lineage plasticity: lymphoid/myeloid lineage potential for CLP and B/T lineage potential for Fr. A. Despite myeloid potential, recombination activating gene 2 reporter activation is first detected at low levels in most MLP cells, with 95% of CLPs showing 10-fold increased levels. Furthermore, single cell analysis shows that half of CLP and 90% of Fr. A cells contain heavy chain DJ rearrangements. These data, together with expression profiles of lineage-specific genes, demonstrate progressive acquisition of B lineage potential and support an asynchronous view of early B cell development, in which B lineage specification initiates in the MLP/CLP stage, whereas myeloid potential is not lost until the pre-pro–B (Fr. A) stage, and B/T lymphoid plasticity persists until the CD19+ pro–B stage. Thus, MLP, CLP, and Fr. A represent progressively B lineage–specified stages in development, before the CD19+ B lineage–committed pro–B stage.

Abbreviations used: CLP, common lymphoid progenitor; DL1, Delta-like 1; FTOC, fetal thymic organ culture; LSK, LIN–Sca1+cKit+; MLP, multilineage progenitor; SCF, stem cell factor.

L.L. Rumfelt's present address is Department of Research and Molecular Biology, Sunnybrook & Women's College Health Science Centre, Toronto, Ontario M4N 3M5, Canada.


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