Studies on Characterization and function of thymic B cells.

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To assess the role of different types of antigen-presenting cells in the induction of tolerance, we isolated B cells, macrophages, and dendritic cells from thymus and spleen, and injected these into neonatal mice across an Mls antigenic barrier. One week after injection of antigen-presenting cells from Mls-incompatible mice or from syngeneic mice, we measured the number of thymic and peripheral Vbeta6^+ T cells (which are reactive to Mls antigen), and the capacity of these cells to induce a graft-vs. -host (GVH) reaction in popliteal lymph nodes of Mls-incompatible mice.Injection of thymic B cells deleted Mls-reactive Vbeta6^+ T cells in the thymus and lymph node, and induced tolerance in the GVH assay. Injection of dendritic cells from spleen or thymus also induced tolerance, but the Vbeta6^+ T cells were anergized rather than deleted. Macrophages from thymus did not induce tolerance. Therefore, these findings clearly indicate that different types of bone marrow-derived Antigen-presenting cells have different capacities for inducing tolerance, and the active cell types (dendritic cells and thymic B cells) can act by distinct mechanisms.