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 Blood, 15 August 2006, Vol. 108, No. 4, pp. 1216-1222.
Prepublished online as a Blood First Edition Paper on May 4, 2006; DOI 10.1182/blood-2005-10-006643.

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HEMATOPOIESIS

Increasing Flt3L availability alters composition of a novel bone marrow lymphoid progenitor compartment

Rhodri Ceredig, Melanie Rauch, Gina Balciunaite, and Antonius G. Rolink

From the Center for Biomedicine, Developmental and Molecular Immunology, Department of Clinical and Biological Sciences (DKBW), University of Basel, Switzerland; and Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 645, Etablissement Français du Sang Bourgogne Franche-Comté, Besançon, France.

We have recently described a CD19– B220+CD117low bone marrow subpopulation with B, T, and myeloid developmental potential, which we have called "early progenitors with lymphoid and myeloid potential" or EPLM. These cells also expressed Fms-like tyrosine kinase 3, Flt3, or CD135. Treatment of mice with the corresponding ligand, Flt3L, showed a 50-fold increase in EPLM. In addition to the expected increase in dendritic cell numbers, Flt3L treatment had a reversible inhibitory effect on B lymphopoiesis. Limiting dilution analysis of sorted EPLM from Flt3L-treated mice showed that B-lymphocyte progenitor activity was reduced 20-fold, but that myeloid and T-cell progenitor activity was largely preserved. EPLM from treated mice transiently reconstituted the thymus and bone marrow of recipient mice, generating cohorts of functional T and B cells in peripheral lymphoid organs. Thus, Flt3L treatment results in a dramatic increase in a novel bone marrow cell with lymphoid and myeloid progenitor activity.


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