Antibody-mediated accommodation of heart grafts expressing an incompatible carbohydrate antigen.
BACKGROUND
Accommodation in patients transplanted with ABO incompatible allografts describes a state in which antibodies are produced against the incompatible blood group carbohydrate antigen; however, the graft is not rejected. The present study describes an experimental model for antibody-mediated accommodation of organs expressing incompatible carbohydrate antigens.


METHODS
The model includes alpha1,3galactosyltransferase knockout mice that lack the alpha-gal epitope (Galalpha1-3Galbeta1-4GlcNAc-R), transplanted heterotopically with wild-type (WT) hearts expressing this epitope. The mice are irradiated and receive memory anti-Gal B cells by adoptive transfer. Immunization of these mice with pig-kidney membranes induces the production of large amounts of anti-Gal, which binds specifically to alpha-gal epitopes.


RESULTS
Under the described accommodation protocol, transplanted mice produce anti-Gal that binds to alpha-gal epitopes on endothelial cells of the grafted WT heart; however, the WT hearts continued to function for months. Second WT hearts transplanted into accommodating, anti-Gal producing mice, were not rejected. Anti-Gal in accommodating mice was not cytolytic, whereas anti-Gal in rejecting mice readily induced complement-mediated lysis of cells expressing alpha-gal epitopes. In addition, accommodating mice displayed a preferential increase in the anti-Gal immunoglobulin (Ig)G2b subclass.


CONCLUSIONS
The immune system may be manipulated to accommodate grafts expressing incompatible carbohydrate antigens by preferential production of noncytolytic anticarbohydrate antibodies.
Mohiuddin
Muhammad M
MM
Department of Cardiovascular-Thoracic Surgery, Rush University, 1653 West Congress Parkway, Chicago, IL 60612, USA.
Ogawa
Haruko
H
Yin
Deng-Ping
DP
Shen
Jikun
J
Galili
Uri
U
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002240:Carbohydrate Sequence; D000939:Epitopes / Q000276:immunology; D005260:Female; D005690:Galactose / Q000276:immunology*; D005700:Galactosyltransferases / Q000235:genetics*; D006084:Graft Rejection / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009101:Multiple Myeloma; D014407:Tumor Cells, Cultured
D000939:Epitopes; D007074:Immunoglobulin G; D005700:Galactosyltransferases; C047006:N-acetyllactosaminide alpha-1,3-galactosyltransferase; D005690:Galactose