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Functions of CD40 and its ligand, gp39 (CD40L)

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Author: Laman, J.D. · Claassen, E. · Noelle, R.J.
Type:article
Date:1996
Institution: TNO Preventie en Gezondheid
Source:Critical Reviews in Immunology, 1, 16, 59-108
Identifier: 233416
Keywords: Biology · Antibody · Autoimmunity · CD40 · CD40 Ligand · Cognate T and B cell interaction · Gp39 · Isotype switching · Lymphocyte activation · Signal transduction · Tolerance · Cd40 antigen · Autoimmunity · B lymphocyte activation · Cell proliferation · Drug receptor binding · gGene switching · Germinal center · Human · Human cell · Immunological tolerance · Immunotherapy · Ligand binding · Lymphocyte activation · Review · Signal transduction · T lymphocyte activation · Animals · Antigens, CD40 · Antigens, Differentiation, T-Lymphocyte · Apoptosis · Autoimmune Diseases · CD40 Ligand · Gene Expression Regulation · Humans · Ligands · Lymphocytes · Membrane Glycoproteins · Mice · Mice, Knockout · Signal Transduction · Structure-Activity Relationship · Tumor Necrosis Factor-alpha

Abstract

Initially, a role for the interaction between CD40, expressed on B cells, and gp39 (CD40L), expressed on activated T cells, has been defined in humoral immunity. CD40-CD40L interaction is an essential signal for B cell proliferation, expression of activation markers, immunoglobulin production, and isotype switching. CD40-CD40L interaction is also required for formation of B memory cells and germinal centers, and signaling through CD40 prevents apoptosis of germinal center B cells. Defective expression of CD40L in humans leads to an inability to produce isotypes other than IgM (hyper IgM syndrome), and to an absence of germinal centers. More recent evidence indicates an expansion of the role of the CD40-CD40L axis in cellular interactions beyond antibody formation. Induced expression of CD40 on monocytes can lead to CD40L-activated monocyte effector mechanisms. In addition, CD40-CD40L interactions are crucially involved in development of autoimmune disease in a number of animal models. CD40-CD40L interactions also impact on growth regulation of certain carcinomas. Manipulation of CD40L has also been used to develop novel strategies for long-term antigen-specific tolerization of peripheral T cells. Finally, the CD40-CD40L axis is involved in thymic selection. Following is a comprehensive overview of CD40L-CD40 interactions in physiological and pathogenic cellular responses and a discussion of the therapeutic ramifications of these interactions. Chemicals/CAS: Antigens, CD40; Antigens, Differentiation, T-Lymphocyte; CD40 Ligand, 147205-72-9; Ligands; Membrane Glycoproteins; Tumor Necrosis Factor-alpha