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Identification of a B-1 B cell–specified progenitor

Abstract

The B-1 subpopulation of B lymphocytes differs phenotypically and functionally from conventional B-2 B cells. B-1 B cells are proposed to derive from a distinct progenitor, but such a population has not been isolated. Here we identify and characterize a B-1 B cell progenitor whose numbers peaked in fetal bone marrow but were less abundant in postnatal bone marrow. These LinCD45Rlo–negCD19+ cells responded to thymic stromal lymphopoietin and 'preferentially' reconstituted functional sIgMhiCD11b+CD5lo–neg B-1 B cells, but not sIgM+CD11b B-2 B cells, in vivo. These data indicate that the CD45Rlo–negCD19+ population includes B-1 B cell–specified progenitors and support models proposing distinct developmental pathways for B-1 B cells.

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Figure 1: Expression of CD45 isoforms by adult bone marrow LinCD45Rlo–negCD19+AA4.1+ cells.
Figure 2: B cell subpopulations in SCID mice reconstituted with adult bone marrow CD45Rlo–negCD19+, CD45R+CD19, or CD45R+CD19+ cells.
Figure 3: Response of adult bone marrow CD45Rlo–negCD19+ cells to TSLP.
Figure 4: B cell development in SCID mice reconstituted with bone marrow CD45Rlo–negCD19+ cells cultured in TSLP.
Figure 5: B cell subpopulations in the peritoneal cavities of Tpte2−/− mice.
Figure 6: Distribution of LinCD45Rlo–negCD19+AA4.1+ and LinCD45R+CD19AA4.1+ cells in fetal and adult bone marrow.
Figure 7: CD45Rlo–negCD19+ progeny secrete anti-phosphorylcholine IgM.

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Acknowledgements

We thank M. Teitell and O. Witte for critical reading of this manuscript. Supported by the National Institutes of Health (AI21256 and HL54850). Four-color flow cytometry analysis and cell sorting were done in the Flow Cytometry Core Facility at the University of California at Los Angeles that is supported by the National Institutes of Health (CA16042).

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Correspondence to Kenneth Dorshkind.

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Supplementary information

Supplementary Fig. 1

LinCD45lo/−CD19+ cells are not contaminated with mature sIgM+ cells. (PDF 142 kb)

Supplementary Fig. 2

Distribution of LinCD45Rlo/−CD19+AA4.1+ and LinCD45R+CD19AA4.1+ cells in the liver of embryos of different ages. (PDF 126 kb)

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Montecino-Rodriguez, E., Leathers, H. & Dorshkind, K. Identification of a B-1 B cell–specified progenitor. Nat Immunol 7, 293–301 (2006). https://doi.org/10.1038/ni1301

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