Mixed hematopoietic chimerism for the simultaneous induction of T and B cell tolerance

Nonmyeloablative induction of mixed hematopoietic chimerism provides a strategy for inducing T cell tolerance across allogeneic and xenogeneic barriers. We have utilized alpha1-3Gal transferase (GalT) knockout mice, which, like humans, produce anti-Gal natural antibodies, to investigate the ability of mixed chimerism to tolerize B cells producing antibodies of this important specificity, which limits xenotransplantation by causing hyperacute and delayed xenograft rejection. Mixed allogeneic or xenogeneic chimerism indeed tolerizes both preexisting anti-Gal-producing B cells and those developing de novo after establishment of mixed chimerism, even in presensitized mice. We present evidence that different mechanisms are involved in the tolerization of the preexisting and newly-developing antibody-secreting cells.