Distinct mechanisms of neonatal tolerance induced by dendritic cells and thymic B cells.

Abstract

SummaryTo assess the role of different types of antigen-presenting cells (APC) in the induction of tolerance, we isolated B cells, macrophages, and dendritic cells from thymus and spleen, and injected these into neonatal BALB/c mice across an Mls-1 antigenic barrier. One week after injection of APC from Mls-I-incompatible mice or from control syngeneic mice, we measured the number of thymic, Mls-1'-reactive, Vs6+ T cells and the capacity of thymocytes to induce a graft-vs .-host (GVH) reaction in popliteal lymph nodes of Mls-1' mice. Injection of thymic but not spleen B cells deleted thymic, Mls-1'-reactive Vs6+ T cells and induced tolerance in the GVH assay. The thymic B cells were primarily of the CD5+ type, and fluorescence-activated cell sorter-purified CD5+ thymic B cells were active. Injection of dendritic cells from spleen or thymus also induced tolerance, but the Vs6 cells were anergized rather than deleted . Macrophages from thymus did not induce tolerance. Dendritic cells and thymic B cells were also effective in inducing tolerance even when injected into Mls -, major histocompatability complex-incompatible, I-E -mice, but only thymic B cells depleted V06-expressing T cells . Therefore, different types of bone marrowderived APC have different capacities for inducing tolerance, and the active cell types (dendritic cells and CD5+ thymic B cells) can act by distinct mechanisms .

TCR Signaling for Initiation and Completion of Thymocyte Positive Selection Has Distinct Requirements for Ligand Quality and Presenting Cell Type

“…The CD4 ϩ CD8 ϩ TCR high precursor thymocytes studied by Kisielow and Miazek (17) appear to correspond to CD69 ϩ CD4 low CD8 low cells (42), and thus the results presented here are fully in accord with the prior data reported by these investigators indicating a need for continued TCR signaling throughout maturation. Barthlott et al, in contrast, reached a different conclusion using reaggregate culture and cells sorted from P14 TCR transgenic mice (14), as did Hare et al in a related system (15).…”

“…DC were purified from disrupted, collagenase-treated spleens of C57BL/6 or B10.BR mice as described previously (42). Briefly, low density cells obtained by BSA gradient centrifugation were cultured in plastic dishes for 1-2 h, after which the nonadherent cells were washed away.…”

Gaucher disease geneGBAfunctions in immune regulation

“…Activated B cells are thought to regulate thymic development either by acting as APCs (22)(23)(24) or by coordinating dendritic cell negative selection (25). Increased activated B cells are seen in the thymus of patients with myasthenia gravis (26).…”

Chemokines: signal lamps for trafficking of T and B cells for development and effector function

“…It is possible that TECK, expressed by thymic medullar dendritic cells, attracts thymocytes and macrophages for co-localization of dendritic cells with thymocytes and macrophages. Thymic dendritic cells are implicated in the negative selection of thymocytes, which eliminates self-antigen reactive thymocytes [34]. Thymic macrophages attracted to TECK have the potential to remove dead thymocytes by scavenging them.…”