PECULIAR IMMUNOBIOLOGY OF BONE MARROW ALLOGRAFTS: II. REJECTION OF PARENTAL GRAFTS BY RESISTANT F1 HYBRID MICE

doi:10.1084/jem.134.6.1513

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PECULIAR IMMUNOBIOLOGY OF BONE MARROW ALLOGRAFTS : II. REJECTION OF PARENTAL GRAFTS BY RESISTANT F₁ HYBRID MICE

Gustavo Cudkowicz M.D.¹ and Michael Bennett M.D.¹

¹ From the Department of Pathology, School of Medicine, State University of New York at Buffalo, Buffalo, New York 14214, and the Department of Experimental Biology, Roswell Park Memorial Institute, Buffalo, New York 14203

F₁ hybrid mice are capable of rejecting inbred parental strainbone marrow grafts after a single lethal exposure to X-rays.The incompatibility is genetically controlled by the Hybrid-histocompatibility-1(Hh-1) locus in or near the D end of the Histocompatibility-2(H-2) region. The onset of parental graft rejection begins 9–12hr after transplantation and is completed by 24 hr. Maturationof hybrid resistance does not occur until the 22nd day of life.In adults, the resistance to parental marrow grafts can be temporarilyabrogated or weakened by administration of cyclophosphamideor dead cultures of Corynebacterium parvum, acute supralethalexposures to radiation, or by split-dose irradiation with 6–37-dayintervals.

Parental marrow grafts elicit a transplantation reactionin irradiated F₁ mice which is indistinguishable from that elicitedin irradiated allogeneic (H-2-incompatible) hosts. Because ofthis immunogenetic similarity, the following question is raised:are the same or different alloantigens responsible for rejectionof parental and allogeneic marrow grafts? In the first case,Hh-1 alleles would be recessive determinants of tissue-specifictransplantation antigens, whereas in the second case they wouldbe the determinants of parental- and tissue-specific antigenssubject to genetic suppression in Hh-1 heterozygotes. Althoughthe available evidence is not conclusive in excluding one ofthe two possibilities, it favors the concept that allograftreactivity to hemopoietic cells is elicited by recessive tissue-specificantigens.

Submitted on July 26, 1971

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