The major barrier to transplantation across discordant species, such as from pig to human, is rejection mediated by xenoreactive natural antibodies (XNA) that bind the carbohydrate epitope Galα1-3Galβ1-4GlcNAc-R (αGal) on donor tissues. This epitope is synthesized by the enzyme glucosyltransferase uridine 5′-diphosphate galactose:β-d-galactosyl-1,4-N-acetyl-d-glucosaminide α(1-3)galactosyltransferase (E.C. 2.4.1.151), or simply αGT. When a functional αGT gene was introduced by retroviral gene transfer into bone marrow cells, αGal XNA production in a murine model ceased. Thus, genetic engineering of bone marrow may overcome humoral rejection of discordant xenografts and may be useful for inducing B cell tolerance.