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Updated: Aug 10, 2026
Generation of Human CD40-activated B cells
Published on: October 17, 2009
Induction of B cell costimulatory function by recombinant murine CD40 ligand
M K Kennedy1, K M Mohler, K D Shanebeck
1Department of Immunobiology, Immunex Research and Development Corporation, Seattle, WA 98101.
Insights
CD40 ligand (CD40L) activates B cells, enhancing their ability to stimulate T cell proliferation. CD40L-activated B cells express B7, contributing to T cell costimulation, but also possess unique costimulatory functions beyond those induced by lipopolysaccharide (LPS).
Area of Science:
- Immunology
- Cellular and Molecular Immunology
- T cell-B cell interactions
Background:
- T cell-dependent B cell regulation relies on CD40-CD40L interactions.
- CD40L on activated T cells interacts with CD40 on B cells.
- B cell costimulatory molecules are crucial for T cell activation.
Purpose of the Study:
- To investigate how recombinant CD40L affects B cell costimulatory function.
- To compare the molecular mechanisms of CD40L- and LPS-induced B cell costimulation.
- To identify novel costimulatory pathways engaged by CD40L-activated B cells.
Main Methods:
- Activation of murine B cells with recombinant membrane-bound CD40L or lipopolysaccharide (LPS).
- Assessment of B cell costimulatory capacity for T cell proliferation (anti-CD3 or alloantigen-dependent).
- Analysis of costimulatory molecule expression (B7, heat-stable antigen [HSA]) and functional blockade using CTLA4.Fc and 20C9 antagonists.
Main Results:
- CD40L-activated B cells, like LPS-activated B cells, costimulate T cell responses.
- LPS enhances both B7 and HSA expression on B cells, contributing to full costimulation.
- CD40L upregulates B7 but not HSA on B cells; costimulation is partially inhibited by blocking B7 and HSA, suggesting an additional CD40L-dependent pathway.
Conclusions:
- CD40L regulates B cell costimulatory function primarily by inducing B7 expression.
- CD40L-activated B cells exhibit unique costimulatory activities not solely dependent on B7 and HSA.
- This study reveals a distinct mechanism of T cell costimulation mediated by CD40L-activated B cells.
Abstract:
T cell-dependent regulation of B cell growth and differentiation involves an interaction between CD40, a B cell surface molecule, and the CD40 ligand (CD40L) which is expressed on activated CD4+ T cells. In the current study, we show that recombinant membrane-bound murine CD40L induces B cells to express costimulatory function for the proliferation of CD4+ T cells. CD40L- or lipopolysaccharide (LPS)-activated, but not control-cultured B cells were strong costimulators of anti-CD3 or alloantigen-dependent T cell responses. The molecular interactions responsible for the increased costimulatory functions were examined by analyzing the activated B cells for changes in the expression of two costimulatory molecules, B7 and heat-stable antigen (HSA), as well as by the use of antagonists of B7 and HSA (CTLA4.Fc and 20C9, respectively). The expression of both B7 and HSA was enhanced on B cells activated with LPS. As observed in previous studies, the costimulatory activity of the LPS-activated B cells was dependent on both B7 and HSA and was completely inhibited in the presence of a combination of CTLA4.Fc and 20C9. In contrast, activation of B cells with CD40L induced the expression of B7 but did not enhance the expression of HSA. In addition the costimulatory activity of the CD40L-activated B cells was partially, but not completely, inhibited by the combination of CTLA4.Fc and 20C9. These results demonstrate that CD40L regulates costimulatory function of B cells in part by inducing the expression of B7 and suggest that CD40L-activated B cells express an additional costimulatory activity that is not associated with LPS-activated B cells.
