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Updated: Aug 8, 2026
Generation of Human CD40-activated B cells
Published on: October 17, 2009
CD40 expression and function in murine B cell ontogeny
E Castigli1, F Young, A M Carossino
1Division of Immunology, Children's Hospital, Boston, MA 02115, USA.
Insights
CD40 antigen is crucial for B cell activation. Its expression and function emerge during B cell development, with bcl-2 influencing pre-B cell responses to CD40 signaling.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- CD40 antigen is a key receptor in the tumor necrosis factor receptor superfamily.
- It is expressed on mature B lymphocytes and is vital for B cell activation, isotype switching, and germinal center formation.
- Understanding CD40's role during B cell development is crucial for immunology research.
Purpose of the Study:
- To investigate CD40 antigen expression and function during mouse B cell development.
- To analyze the impact of specific genetic modifications on B cell development and CD40 signaling.
- To determine the stage-specific roles of CD40 in B cell maturation.
Main Methods:
- Analysis of CD40 expression and function in normal mice.
- Utilizing transgenic mouse models with arrested B cell development (RAG-2-/-).
- Examining transgenic mice with altered expression of mu heavy chain and/or bcl-2 proto-oncogene.
Main Results:
- CD40 antigen was not detected on pro-B cells but was expressed at low levels on pre-B cells.
- Pre-B cells did not respond to CD40 triggering (CD23 expression or proliferation with IL-4).
- Overexpression of bcl-2 increased CD40 density on pre-B cells, enabling response to CD40 ligation.
Conclusions:
- CD40 expression and functional responsiveness are acquired during B cell development.
- The bcl-2 proto-oncogene significantly modulates CD40 expression density and functional responses in pre-B cells.
- These findings provide insights into the intricate regulation of B cell activation and development.
Abstract:
The CD40 antigen, a member of the nerve growth factor/tumor necrosis factor receptor family, is expressed on all mature B lymphocytes and plays a crucial role in B cell activation, T cell-dependent antigen-driven isotype switching and germinal center formation. We have analyzed CD40 expression and function during mouse B cell development by examining B cell precursors in normal mice and in transgenic animals in which B cell development is frozen at discrete stages. These models included RAG-2-/- mice, and transgenic littermates that express a mu heavy chain and/or the bcl-2 proto-oncogene transgene. CD40 was undetectable at the pro-B cell stage, but was expressed, although at low levels, on pre-B cells. However, pre-B cells failed to respond to CD40 triggering either by expression of CD23 or by proliferation in the presence of IL-4. Overexpression of bcl-2 increased the density of CD40 expression on pre-B cells: these cells respond to CD40 ligation by expressing CD23 and by proliferating in the presence of IL-4.
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