BONE MARROW-DERIVED CELLS ARE RESPONSIBLE FOR STIMULATING I REGION-INCOMPATIBLE SKIN GRAFT REJECTION

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Abstract
By using bone marrow radiation chimeras as skin graft donors, the relative contribution of B cells to allograft immunogenicity in both I region only and whole H-2-disparate strain combinations was evaluated. When grafted on A.TH mice, skin from A.TH .fwdarw. A.TL bone marrow chimera donors showed markedly prolonged survival times compared with normal A.TL skin, A.TL .fwdarw. A.TL skin or skin from irradiated A.TL mice A.TH .fwdarw. A.TL skin was accepted indefinitely on (A.TH .times. B10)F1 mice; normal A.TL skin was promptly rejected. Thus, in the I region-only-disparate strain combinations, the B cell in donor skin appears to be entirely responsible for skin graft immunogenicity. A lack of epidermal specific histocompatibility antigens mapping in the I region was indicated. Skin from A .fwdarw. (B6 .times. A)F1 chimeras was rejected in the same time as normal (B6 .times. A)F1 skin when grafted onto A mice. Immunoprecipitation and polyacrylamide gel electrophoresis of epidermal Ia confirmed that host Ia+ cells were absent in A .fwdarw. (B6 .times. A)F1 skin. Allogeneic B Ia+ cells apparently are not required in donor skin for allograft immunogenicity across whole H-2 differences. Graft rejection of chimeric skin could not be induced by creating chimeras whose skin was compatible, but bone marrow incompatible (whole H-2 or I region only) with the skin graft recipient. Ia+ cells in donor skin apparently are sufficient by themselves, but not necessarily required for allograft immunogenicity if appropriate antigenic differences are expressed on the remainder of the epidermal cells. These results are consistent with current evidence implicating the Langerhans cells as the relevant B cell responsible for skin graft immunogenicity.