PMID: 9547344May 23, 1998Paper

Tolerization of anti-Galalpha1-3Gal natural antibody-forming B cells by induction of mixed chimerism

The Journal of Experimental Medicine
Y G YangM Sykes

Abstract

Xenotransplantation could overcome the severe shortage of allogeneic organs, a major factor limiting organ transplantation. Unfortunately, transplantation of organs from pigs, the most suitable potential donor species, results in hyperacute rejection in primate recipients, due to the presence of anti-Galalpha1-3Gal (Gal) natural antibodies (NAbs) in their sera. We evaluated the ability to tolerize anti-Gal NAb-producing B cells in alpha1,3-galactosyltransferase knockout (GalT KO) mice using bone marrow transplantation (BMT) from GalT+/+ wild-type (WT) mice. Lasting mixed chimerism was achieved in KO mice by cotransplantation of GalT KO and WT marrow after lethal irradiation. The levels of anti-Gal NAb in sera of mixed chimeras were reduced markedly 2 wk after BMT, and became undetectable at later time points. Immunization with Gal+/+ xenogeneic cells failed to stimulate anti-Gal antibody production in mixed chimeras, whereas the production of non-Gal-specific antixenoantigen antibodies was stimulated. An absence of anti-Gal-producing B cells was demonstrated by enzyme-linked immunospot assays in mixed KO + WT --> KO chimeras. Thus, mixed chimerism efficiently induces anti-Gal-specific B cell tolerance in addition to T cell tole...Continue Reading

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Citations

Aug 11, 2000·Transplantation Proceedings·J L Platt
Aug 11, 2000·Transplantation Proceedings·Y XuA D Thall
Dec 29, 1998·Transplantation Proceedings·M SykesY G Yang
Mar 15, 2000·Transplantation Proceedings·G L XiaM Waer
Sep 10, 2003·Experimental Hematology·Annie C Le GuernYong-Guang Yang
Jun 17, 2000·Current Opinion in Immunology·K Hayakawa, R R Hardy
Oct 6, 1999·Current Opinion in Immunology·M S Sandrin, I F McKenzie
Aug 16, 2002·Transplant Immunology·D ChenJ S Bromberg
Dec 22, 2000·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·D K CooperUNKNOWN Xenotransplantation Advisory Committee of the International Society for Heart and Lung Transplantation
Jun 7, 2005·Nature Medicine·Robert I LechlerLaurence A Turka
Jun 16, 2007·Nature Reviews. Immunology·Yong-Guang Yang, Megan Sykes
Jan 8, 2000·Clinical and Experimental Pharmacology & Physiology·J L Platt, T Nagayasu
Feb 24, 2001·Transplantation·W ParkerJ L Platt
Jun 4, 2002·Transplantation·Nathalie Cretin, John Iacomini
Jul 20, 2002·Transplantation·Masahiro TanemuraUri Galili
Feb 1, 2003·Annals of Surgery·William E BeschornerAlan N Langnas
Feb 9, 2005·Transplantation·Kathryn J Wood
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Dec 16, 1998·Xenotransplantation·M Koulmanda, H Auchincloss
Jun 29, 2007·International Archives of Allergy and Immunology·Ines PreeThomas Wekerle

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