Thymic Dendritic Cells and B Cells: Isolation and Function

Abstract

The thymus is the primary organ in which T cells undergo rearrangement of T cell receptor α and β genes, positive selection for affinity to self MHC products, and elimination (negative selection) of reactivity to self antigens. These events require an interaction of the developing T cell with other cell types in the thymus. The latter include epithelial cells, macrophages, dendritic cells, and the recently described thymic B cells the majority of which are CD5⁺. Here we review the identification and isolation of thymic dendritic cells and CD5⁺ B cells. We consider phenotype, ontogeny, and function, including possible contributions to the induction of self tolerance. Thymic dendritic cells are similar to spleen dendritic cells, but are larger and exhibit a few differences in phenotype. Dendritic cells from both organs are equally potent accessory cells for the MLR and lectin-induced, T cell proliferation. Thymic dendritic cells have higher levels of Fc receptors and support anti-CD3 dependent mitogenesis. Thymic CD5⁺ B cells share phenotypic features with peritoneal CD5⁺ B cells. However thymic B cells neither proliferate nor form antibody producing cells in response to the stimulation with LPS or anti-IgM plus IL-4, but do respond to stimulation with MHC class II-restricted helper T cells. Thymic dendritic cells and CD5⁺ B cells both appear at a similar time in ontogeny, about 14 d of gestation, which is the time T cell differentiation begins to take place. Dendritic cells from spleen, which are potent activators for peripheral T cells, are also potent inactivators for thymic-derived cytotoxic T cells. A correlation between reactivity to MIs products and the expression of TCR-Vβ genes is well documented, and B cells are the primary APC for this antigen. Therefore, thymic CD5⁺ B cells may be a good tool for the investigation of tolerance to Mls products.

Key Words:

• anergy
• CD5⁺ B cells
• clonal deletion
• Mls
• tolerance
• thymus