CD40 Ligand Expression Is Developmentally Regulated in Human Thymocytes

Thymic selection involves the interaction between developing thymocytes and the thymic microenvironment. CD40 is expressed on thymic epithelial cells and on bone marrow-derived antigen-presenting cells in the thymus. We have investigated the capacity of human thymocytes to express CD40 ligand. CD40 ligand was not detectable on resting immature double-positive (CD4⁺/CD8⁺) or resting mature single-positive (CD4⁺/CD8^- or CD4^-/CD8⁺) thymocytes. Immature thymocytes failed to express CD40 ligand on their surface after stimulation with PMA and ionomycin, whereas stimulated CD4⁺/CD8^- mature thymocytes expressed CD40 ligand. Northern blot analysis revealed that CD40 ligand mRNA was detectable in activated mature single-positive thymocytes. CD40 ligand expression by mature thymocytes was associated with the capacity to drive immunoglobulin isotype switching in purified B cells. These results demonstrate that the ability to express CD40 ligand is acquired late in thymocyte development and that mature thymocytes are capable of providing B cells with the activation signals necessary for immunoglobulin isotype switching.