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Updated: Aug 10, 2026
Murine Model of CD40-activation of B cells
Published on: March 6, 2010
CD73 expression and fyn-dependent signaling on murine lymphocytes
Y Yamashita1, S W Hooker, H Jiang
1Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Insights
The study characterizes CD73 (cluster of differentiation 73) in mice, revealing its expression on mature lymphocytes and its role in T cell signaling. CD73 also appears crucial for lymphocyte-stromal cell interactions in lymphoid tissues.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- CD73, a glycosyl phosphatidylinositol-anchored protein, possesses ecto-enzyme and signal transducing functions in human T lymphocytes.
- Murine CD73 distribution and function were previously uncharacterized due to a lack of specific antibodies.
Purpose of the Study:
- To analyze the distribution and function of CD73 in murine lymphoid tissues.
- To investigate the role of CD73 in lymphocyte maturation, activation, and stromal interactions.
Main Methods:
- Development of the first monoclonal antibodies (mAb) specific for murine CD73.
- Immunohistochemical analysis of CD73 expression in murine lymphoid tissues.
- Analysis of T cell proliferation and IL-2 secretion upon CD73 ligation in Fyn-/- mice.
Main Results:
- CD73 expression increases with lymphocyte maturation in both T and B cells, particularly in isotype-switched B cells.
- CD73 ligation, in conjunction with PMA, induces T cell proliferation and IL-2 secretion, dependent on the tyrosine kinase Fyn.
- CD73 is highly expressed on thymic and lymphoid stromal cells, suggesting a role in lymphocyte-stromal interactions.
Conclusions:
- CD73 plays a conserved role in T cell activation and signal transduction, requiring Fyn kinase.
- CD73 expression on stromal cells indicates a potential function in modulating the local microenvironment for lymphocyte development and function.
- CD73's down-regulation after antibody cross-linking suggests ligand-mediated regulation.
Abstract:
CD73 is a glycosyl phosphatidylinositol-anchored protein with both ecto-enzyme activity (ecto-5'-nucleotidase) and signal transducing capabilities for human T lymphocytes. We now report an analysis of the distribution and function of CD73 in murine lymphoid tissues made possible by the development of the first monoclonal antibodies (mAb) specific for murine CD73. Subsets of T and B lymphocytes are CD73+ and the level of expression increases with lymphocyte maturation in both species. Among B cells, CD73 is largely restricted to cells which have undergone isotype switching. The signal transmitting function of CD73 is also conserved, as splenic T cells treated with anti-CD73 mAb plus phorbol 12-myristate 13-acetate proliferate and secrete IL-2. Fyn-/- mice are unresponsive to CD73 ligation, however, demonstrating the requirement for this tyrosine kinase in CD73-mediated signal transduction. CD73 is down-regulated after mAb plus cross-linking, suggesting that expression may be controlled by interaction with a ligand. Only small numbers of thymocytes are CD73+, so CD73 receptor functions are unlikely to be important for developing T cells. However, immunohistochemical analysis reveals that reticular and vascular cells throughout the thymus and other lymphoid tissues are markedly CD73+. Therefore, CD73 might mediate lymphocyte-stromal cell interactions or condition the local microenvironment to facilitate lymphocyte development and/or function.
