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Updated: Sep 30, 2026
Generation of Human CD40-activated B cells
Published on: October 16, 2009
Cutting edge: CD40 ligand is a limiting factor in the humoral response to T cell-dependent antigens
M Pérez-Melgosa1, D Hollenbaugh, C B Wilson
1Department of Immunology, University of Washington, Seattle 98195, USA.
Insights
Increased CD40 ligand (CD40L) expression in transgenic mice accelerated T-dependent B cell responses. This suggests CD40L is a limiting factor in high-affinity antibody production and class switching.
Area of Science:
- Immunology
- Molecular Biology
Background:
- CD40 ligand (CD40L) is vital for T cell-dependent B cell responses.
- The role of CD40L abundance as a limiting factor in B cell development remains unclear.
Purpose of the Study:
- To investigate the impact of increased CD40L expression on T cell-dependent B cell responses.
- To determine if CD40L abundance limits antibody production and class switching.
Main Methods:
- Generation of transgenic mice (CD40Ltg+) with increased CD40L expression under the IL-2 promoter.
- Analysis of surface CD40L and mRNA levels in activated T cells.
- Assessment of antibody titers and affinity in response to T-dependent and T-independent antigens.
Main Results:
- CD40Ltg+ mice showed a modest increase in activated T cells with detectable surface CD40L and higher CD40L mRNA levels.
- Transgenic mice developed higher titers of high-affinity IgG and IgG1 antibodies against T-dependent antigens.
- Antibody responses to T-independent antigens were similar between transgenic and control mice.
Conclusions:
- A modest increase in CD40L expression accelerates T-dependent B cell responses.
- CD40L plays a limiting role in the induction of high-affinity antibodies and antibody-class switching.
Abstract:
CD40 ligand (CD40L) plays a crucial role in T cell-dependent B cell responses, but whether its abundance is a limiting factor in their development is unclear. This question was addressed in transgenic mice expressing the murine CD40L gene under the control of the IL-2-promoter (CD40Ltg+). The fraction of activated T cells from the CD40Ltg+ mice with detectable levels of surface CD40L was modestly greater (1.1- to 2-fold) than littermate controls and paralleled an approximately 1.8-fold increase in CD40L mRNA abundance. In response to trinitrophenol (TNP)-keyhole limpet hemocyanin and tetanus/diphtheria vaccine, CD40Ltg+ mice developed higher titers of high-affinity IgG and IgG1 Ab than wild-type mice. In contrast, the Ab response of CD40Ltg+ and control mice was similar in response to the T-independent Ag TNP-Ficoll. These results suggest that a modest increment in expression of CD40L accelerates the development of T-dependent responses, and that CD40L plays a limiting role in the induction of high-affinity Ab and Ab-class switching.
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