The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/2/735/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 4, February 15, 1999 735-740

Brief Definitive Reports

Commitment to the B Lymphoid Lineage Occurs before DH-JH Recombination

David Allman, Jin Li, and Richard R. Hardy

From the Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111

Lineage commitment in B lymphopoiesis remains poorly understood due to the inability to clearly define newly committed B lineage progenitors and their multipotential descendants. We examined the potential of three recently described progenitor populations in adult mouse bone marrow to differentiate into each hematopoietic lineage. The earliest of these, termed fraction (Fr.) A0, exhibited myeloid, erythroid, and B and T lymphoid progenitor activity and included individual cells with myeloid/B lymphoid potential. In sharp contrast, two later populations, termed Frs. A1 and A2 and characterized by surface B220 expression and transcription of the germline immunoglobulin heavy chain (IgH) locus, lacked progenitor activity for all hematopoietic lineages except B lymphocytes. These observations, together with single cell polymerase chain reaction analysis showing a lack of DHJH rearrangements in each population and experiments showing identical precursor potentials when these populations were derived from recombination activating gene (Rag)-1–/– and JH–/– mice, demonstrate that commitment to the B lymphoid lineage occurs before and independently of VHDHJH recombination.

Key Words: lineage restriction • B lymphopoiesis • progenitor • hematopoiesis • stem cell

Address correspondence to David Allman, Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA 19111. Phone: 215-728-2463; Fax: 215-728-2412; E-mail: DM_Allman{at}fccc.edu

The authors wish to acknowledge the expert technical assistance of Ms. Susan Shinton, and thank Dr. Avinash Bhandoola for instruction in intrathymic transfers. We also thank Drs. Michael Cancro, Dietmar Kappes, Jennifer Punt, and David Wiest for critical review of this manuscript.


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