B cell-induced tolerance to class II MHC antigens in the chicken

Transplantation of cells from the bursa of Fabricius reconstitutes the B cell system of chemically bursectomized chickens. Even allogeneic bursa cells can restore the recipient's B cell system and induce tolerance to donor major histocompatibility complex antigens, but the chimeras cannot mount a T-dependent antibody response. In order to study the mechanisms of tolerance to class II MHC (B-L) antigens, we transplanted class II-incompatible bursa cells from 4-day-old donors into cyclophosphamide-treated recipients of the same age. Donor and host cells carried different allelic products of a genetically polymorphic B cell alloantigen (Bu-1), allowing us to detect cellular chimerism using monoclonal antibodies and immunofluorescence. The B cell-chimeric chickens were tested for tolerance by skin grafting, graft-versus-host splenomegaly assay, and mixed lymphocyte reaction. Specific unresponsiveness to donor MHC antigens was observed in all three tests. When spleen cells from chickens tolerant of donor class II antigens were transferred into irradiated secondary recipients of the same strain, several of the secondary recipients accepted primary donor-type skin grafts. Most secondary recipients were, however, reactive in the GVH assay and MLR. Depletion of chimeric B cells before spleen cell transfer impaired the transferability of tolerance to class II disparity. Altogether, our results indicate that tolerance to class II antigens can be induced with B cells. They suggest that at least two different mechanisms maintain the unresponsiveness in B cell-chimeric chickens.