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Updated: Aug 8, 2026
Murine Model of CD40-activation of B cells
Published on: March 6, 2010
CD10/NEP is expressed on Thy-1low B220+ murine B-cell progenitors and functions to regulate stromal cell-dependent
G Salles1, C Y Chen, E L Reinherz
1Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115.
Insights
The common acute lymphoblastic leukemia antigen (CALLA; CD10, neutral endopeptidase 24.11, NEP) is expressed on early B-cell progenitors. Inhibiting CD10/NEP enhances stromal cell-dependent B lymphopoiesis in vitro.
Area of Science:
- Immunology
- Hematopoiesis
- Cell Biology
Background:
- The common acute lymphoblastic leukemia antigen (CALLA), also known as CD10 or neutral endopeptidase 24.11 (NEP), plays a role in lymphoid development.
- Understanding CD10/NEP function in early lymphoid development is crucial for characterizing B-cell ontogeny.
Purpose of the Study:
- To investigate the expression of CD10/NEP in murine lymphoid progenitors.
- To analyze the functional impact of CD10/NEP inhibition on in vitro lymphoid differentiation.
Main Methods:
- Identification and isolation of murine lymphoid progenitors expressing CD10/NEP from bone marrow and Whitlock-Witte cultures.
- Analysis of CD10/NEP transcripts and enzymatic activity in different cell populations.
- In vitro differentiation assays using specific CD10/NEP inhibitors.
Main Results:
- CD10/NEP expression was primarily detected in pro-B cells and bone marrow stromal cells supporting B-lymphoid progenitor development.
- Abelson and H-ras transformed pre-B-cell lines, as well as later B-cell progenitors, lacked CD10/NEP expression.
- Inhibition of CD10/NEP significantly increased lymphoid colony formation in stromal cell-dependent cultures by 34%.
Conclusions:
- CD10/NEP expression on murine pro-B cells and bone marrow stromal cells suggests a role in early B-cell ontogeny.
- CD10/NEP appears to regulate the earliest stages of stromal cell-dependent B lymphopoiesis.
Abstract:
To further characterize the function of the common acute lymphoblastic leukemia antigen (CALLA; CD10, neutral endopeptidase 24.11, NEP) in early lymphoid development, we have identified murine lymphoid progenitors expressing CD10/NEP and analyzed the effects of inhibiting the enzyme in in vitro assays of murine lymphoid differentiation. CD10/NEP transcripts and enzymatic activity were primarily restricted to the subpopulation of murine lymphoid progenitors, termed pro-B cells, which were isolated from bone marrow (BM) and modified Whitlock-Witte cultures and defined by coexpression of B220 and low levels of Thy-1. CD10/NEP transcripts and cell surface enzymatic activity were also detected in BM stromal cells known to support the development of B-lymphoid progenitors. In contrast, Abelson and H-ras transformed pre-B-cell lines were CD10/NEP- as were Thy-1-B220+ pre-B cells from BM and modified Whitlock-Witte cultures and Thy-1lowLin- (B220-Mac-1-GR-1-Ly-2/3-) uncommitted hematopoietic progenitors from BM. The expression of CD10/NEP on murine pro-B cells and BM stromal cells suggests a role for the enzyme in early B-cell ontogeny. In modified Whitlock-Witte cultures in which Thy-1lowLin- progenitors plated on BM stromal cells differentiate into Thy-1lowB220+ pro-B and Thy-1-B220+ pre-B cells, the addition of specific CD10/NEP inhibitors increased the number of lymphoid colonies at days 5 through 7 by 34% (P < .001). The results suggest that CD10/NEP participates in the regulation of the earliest stages of stromal cell-dependent B lymphopoiesis.
