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Dynamics and localization of early B-lymphocyte precursor cells (pro-B
cells) in the bone marrow of scid mice
DG Osmond, N Kim, R Manoukian, RA Phillips, SA Rico-Vargas and K Jacobsen
Department of Anatomy, McGill University, Montreal, Quebec, Canada.
Mice homozygous for the scid (severe combined immunodeficiency) mutation
are generally unable to produce B lymphocytes, a condition attributed to
defective rearrangement of immunoglobulin genes in precursor B cells. Some
early B-lineage cells are present in the bone marrow (BM), however. In scid
mice, we defined three subsets of early progenitor B cells lacking mu heavy
chains (pro-B cells) based on the expression of terminal deoxynucleotidyl
transferase (TdT) and B220 glycoprotein: (a) early pro-B cells (TdT+B220-),
(b) intermediate pro-B cells (TdT+B220+), and (c) late pro-B cells
(TdT-B220+). Double immunofluorescence labeling of BM cell suspensions has
shown normal numbers of early and intermediate pro-B cells, substantially
reduced numbers of late pro-B cells, and an absence of pre-B cells and B
cells. Early and intermediate pro-B cells accumulated in metaphase in near-
normal numbers after intraperitoneal (IP) vincristine administration. B220+
pro-B cells have been localized in BM sections by the binding of
intravenously (IV) administered 125I monoclonal antibody (MoAb) 14.8,
detected by light and electron microscope radioautography. Many B220+ cells
were located peripherally in the bone-lining cell layers associated with
stromal reticular cells. More centrally located B220+ cells were frequently
associated with macrophages containing prominent cytoplasmic inclusions.
Occasional B220+ cells were present in venous sinusoids. These results
demonstrate that many pro-B cells in scid mice occupy microenvironments in
the BM near the surrounding bone. The pro-B cells maintain normal rates of
production during stages of presumptive mu heavy-chain gene rearrangement,
apparently unaffected by the absence of a mature B cell pool. Nearly all
defective cells then abort at the late pro-B cell stage and are deleted,
apparently by macrophages. The findings contribute to models of in vivo
differentiation, regulation, localization, and selection of early B-lineage
cells in the BM.
Volume 79,
Issue 7,
pp. 1695-1703,
04/01/1992
Copyright © 1992 by The American Society of Hematology

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