The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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J. Exp. Med.
© The Rockefeller University Press
0022-1007/96/12/2217/14 $2.00
Volume 184 December 1996 2217-2230

Ordering of Human Bone Marrow B Lymphocyte Precursors by Single-Cell Polymerase Chain Reaction Analyses of the Rearrangement Status of the Immunoglobulin H and L Chain Gene Loci

By Paolo Ghia,* Edwin ten Boekel,* Eva Sanz,Dagger § Antonio de la Hera,Dagger § Antonius Rolink,* and Fritz Melchers*

From the * Basel Institute for Immunology, CH-4005 Basel, Switzerland; Dagger  Centro de Investigaciones Biologicas, E-28006 Madrid, Spain; and § Department of Medicine, Alcala University, E-28871 Madrid, Spain

CD19+CD10+ human B lineage bone marrow cells were separated into cycling or resting cells, which differ in their expression of CD34, VpreB, recombination activating gene (RAG-1), and terminal deoxynucleotidyl transferase (TdT). Polymerase chain reaction analyses developed for DHJH and Vkappa Jkappa , Vkappa Jkappa K(de) and Vkappa K(de) rearrangements with DNA of single cells and a comparison with B lineage cell development in mouse bone marrow, allow to delineate the human B lymphocyte pathway of development as follows: CD34+VpreB+RAG-1+TdT+, DHJH-rearranged, kappa L germline cycling pre-B I cells right-arrow CD34-VpreB+µH chain+ (pre-B receptor+) RAG-1-TdT-, VHDHJH-rearranged, kappa L germline, cycling pre-B II cells right-arrow CD34-VpreB-, intracytoplasmic µH chain+ (pre-B receptor-) RAG-1+/- TdT-, VHDHJH-rearranged, mainly kappa L germline cycling pre-B II cells right-arrow CD34-VpreB- intracytoplasmic µH chain+, RAG-1+TdT-, VHDHJH-rearranged, Vkappa Jkappa -rearranged, IgM-, resting pre-B II cells CD34+VpreB-, sIgM+, RAG-1+TdT-, VHDHJH- and Vkappa Jkappa -rearranged IgM+ immature B cells right-arrow CD34-, CD10-, sIgM+/sIgD+ mature B cells. This order, for the first time established for human B lineage cells, shows striking similarities with that established for mouse B lineage cells in bone marrow.


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