Anti-galactose-alpha(1,3) galactose antibody production in alpha1,3-galactosyltransferase gene knockout mice after xeno and allo transplantation.
Antibodies (Abs) that mediate the hyperacute rejection and acute vascular rejection/delayed xenograft rejection of pig organs in humans and Old World primates are predominantly directed at a single carbohydrate epitope, galactose-alpha1,3-galactose (alpha1,3Gal). The T-cell dependence of elicited anti-alpha1,3Gal Ab responses in humans and Old World primates is controversial. In this study we have characterized anti-alpha1,3Gal Ab production in mice with disrupted alpha1,3-galactosyltransferase genes (GT-Ko mice) and determined the T-cell dependence of anti-alpha1,3Gal Ab responses, following xenograft and allograft transplantation. GT-Ko mice produce natural anti-alpha1,3Gal IgM and IgG in an age-dependent manner, however, these Abs could not elicit hyperacute rejection nor affect the rate of cardiac xenograft (3-5 days) or allograft rejection (7-9 days). Transplantation of xenogeneic Lewis rats hearts elicited modest anti-alpha1,3Gal Ab, but vigorous xenoAb responses. The anti-alpha1,3Gal Ab response was restricted to the IgM and IgG3 subclass while the xenoAb response comprised IgM and all four IgG subclasses. Transplantation of allogeneic C3H hearts elicited weak anti-alpha1,3Gal Ab responses that were primarily IgM, but vigorous alloAb responses. Despite the restriction of elicited anti-alpha 1,3Gal Ab responses to the IgM and IgG3 isotypes, these responses are T-cell dependent. The ability of allografts to elicit weak anti-alpha1,3Gal but strong allo-Ab responses, can be explained by the dependence of alpha1,3Gal-specific B cells on cognate help from T cells.
Chong
A
A
Department of General Surgery, Rush Presbyterian St. Luke's Medical Center, Chicago, IL 60612, USA. achong@rush.edu
Blinder
L
L
Ma
L
L
Yin
D
D
Shen
J
J
Williams
J W
JW
Byrne
G
G
Schwarz
A
A
Diamond
L S
LS
Logan
J E
JE
D000367:Age Factors; D000818:Animals; D000910:Antibodies, Heterophile / Q000096:biosynthesis*; D004187:Disaccharides / Q000276:immunology*; D005700:Galactosyltransferases / Q000235:genetics / Q000502:physiology*; D006084:Graft Rejection; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D051381:Rats; D011917:Rats, Inbred Lew; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
D000910:Antibodies, Heterophile; D004187:Disaccharides; C055075:galactosyl-(1-3)galactose; D005700:Galactosyltransferases