1998
DOI: 10.1084/jem.187.8.1335
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Tolerization of Anti–Galα1-3Gal Natural Antibody–forming B Cells by Induction of Mixed Chimerism

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–Galα1-3Gal (Gal) natural antibodies (NAbs) in their sera. We evaluated the ability to tolerize anti-Gal NAb–producing B cells in α1,3-galactosyltransferase knockout (GalT KO) mice using bone marrow transplantation… Show more

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Cited by 183 publications
(148 citation statements)
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“…Inducing molecular chimerism results in the same stable and specific tolerance to αGal established following induction of mixed cellular chimerism. 11,26 We suggest that similar approaches could be used to prevent rejection of ABO incompatible allotransplants and autoimmune diseases.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Inducing molecular chimerism results in the same stable and specific tolerance to αGal established following induction of mixed cellular chimerism. 11,26 We suggest that similar approaches could be used to prevent rejection of ABO incompatible allotransplants and autoimmune diseases.…”
Section: Discussionmentioning
confidence: 99%
“…11 Indeed, it has been known for many years that a state of mixed (donor and host) hematopoietic chimerism, induced by bone marrow transplantation, can lead to permanent tolerance of T and B cells across allogeneic and concordant xenogeneic species barriers. [12][13][14][15][16][17] However, because bone marrow transplantation across discordant xenogeneic barriers has not yet been successful for a variety of reasons, this approach is not clinically applicable as a means of inducing tolerance to αGal.…”
Section: Introductionmentioning
confidence: 99%
“…For analysis of anti-aGal nAb, rabbit red blood cells (RRBC) were used as described previously [17]. To analyze anti-aGal Abs after the immunization with 1 Â 10 9 RRBC, SC from SCID mice were used [6]. Sera were taken from GalT -/-recipients at each time points.…”
Section: Methodsmentioning
confidence: 99%
“…B-cell tolerance against xenogenic antigens including nAb has been induced in rats treated with cyclosporine plus Leflunomide [3] or CVF [4]. On the other hand, the Sykes' group have demonstrated the efficacy of mixed chimeric approach in the induction of B-cell as well as T-cell tolerance by using major histocompatibility complex (MHC)-disparate wild-type (GalT þ/þ ) and GalT -/-mice [5,6].…”
Section: Introductionmentioning
confidence: 99%
“…We (34) and others (41) have shown that hamster RBC express xenoantigens recognized by rat anti-hamster IgM and IgG Abs at a level quantitatively and qualitatively comparable with that expressed on hamster PBMC. The advantage of using RBC as target cells is the decrease in nonspecific binding by Abs via cell surface Ig and Fc receptors (34,42). Fig.…”
Section: Abs and Complement Activitymentioning
confidence: 99%