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CD40 ligand/CD40 deficiency
E Castigli1, R Fuleihan, N Ramesh
1Division of Immunology, Children's Hospital, Boston, MA 02115, USA.
Insights
The interaction between CD40 and CD40 ligand is crucial for B cell isotype switching. Defects in CD40 or CD40L prevent switching from IgM to other antibodies, impacting immune responses.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- CD40 is a B cell surface antigen, and its ligand (CD40L) is found on activated T cells.
- The CD40-CD40L interaction is essential for B cell proliferation and antibody isotype switching in T-cell-dependent immune responses.
Purpose of the Study:
- To investigate the role of CD40 and CD40L in B cell isotype switching.
- To understand the consequences of CD40L gene defects in X-linked hyper-IgM syndrome (HIGMX-1).
- To examine the effects of CD40 gene disruption in mice on immune responses.
Main Methods:
- Analysis of patients with X-linked hyper-IgM syndrome (HIGMX-1) with CD40L gene mutations.
- Generation and study of mice with a disrupted CD40 gene.
Main Results:
- Patients with HIGMX-1 exhibit a failure to switch from IgM to IgG, IgA, and IgE.
- Mice with disrupted CD40 genes cannot perform isotype switching to T-cell-dependent antigens.
- Mice with disrupted CD40 genes maintain normal responses to T-cell-independent antigens.
Conclusions:
- The CD40-CD40L pathway is indispensable for T-cell-dependent B cell isotype switching.
- Disruptions in CD40 or CD40L lead to specific immunodeficiencies characterized by impaired antibody class switching.
Abstract:
CD40 is a surface antigen expressed on B cells. The CD40 ligand (CD40L) is expressed on activated T cells. Interaction between CD40 and CD40L is critical for proliferation and isotype switching in the context of a response to a T-cell-dependent antigen. Patients with X-linked hyper-IgM syndrome (HIGMX-1) in their CD40L gene are unable to switch from IgM to IgG, IgA and IgE. Mice with a disrupted CD40 gene fail to undergo isotype switching to T-cell-dependent antigens but respond normally to T-independent antigens.