TY - JOUR
T1 - Anti-galactose-α(1,3) galactose antibody production in α1,3-galactosyltransferase gene knockout mice after xeno and allo transplantation
AU - Chong, Anita S.F.
AU - Blinder, Leonard
AU - Ma, Lianli
AU - Yin, Dengping
AU - Shen, Jikun
AU - Williams, James W.
AU - Byrne, Gerry
AU - Schwarz, Alex
AU - Diamond, Lisa S.
AU - Logan, John E.
N1 - Funding Information:
This work was supported by grants from the NIH (AI034061) and Nextran Corp.We thank Drs Janet Plate and Uri Galili for reading of this manuscript and for their helpful comments.
PY - 2000
Y1 - 2000
N2 - 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-α1,3-galactose (α1,3Gal). The T-cell dependence of elicited anti-α1,3Gal Ab responses in humans and Old World primates is controversial. In this study we have characterized anti-α1,3Gal Ab production in mice with disrupted α1,3-galactosyltransferase genes (GT-Ko mice) and determined the T-cell dependence of anti-α1,3Gal Ab responses, following xenograft and allograft transplantation. GT-Ko mice produce natural anti-α1,3Gal 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-α1,3Gal Ab, but vigorous xenoAb responses. The anti-α1,3Gal 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-α1,3Gal Ab responses that were primarily IgM, but vigorous alloAb responses. Despite the restriction of elicited anti-α1,3Gal Ab responses to the IgM and IgG3 isotypes, these responses are T-cell dependent. The ability of allografts to elicit weak anti-α1,3Gal but strong allo-Ab responses, can be explained by the dependence of α1,3Gal-specific B cells on cognate help from T cells. (C) 2000 Elsevier Science S.A. All rights reserved.
AB - 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-α1,3-galactose (α1,3Gal). The T-cell dependence of elicited anti-α1,3Gal Ab responses in humans and Old World primates is controversial. In this study we have characterized anti-α1,3Gal Ab production in mice with disrupted α1,3-galactosyltransferase genes (GT-Ko mice) and determined the T-cell dependence of anti-α1,3Gal Ab responses, following xenograft and allograft transplantation. GT-Ko mice produce natural anti-α1,3Gal 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-α1,3Gal Ab, but vigorous xenoAb responses. The anti-α1,3Gal 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-α1,3Gal Ab responses that were primarily IgM, but vigorous alloAb responses. Despite the restriction of elicited anti-α1,3Gal Ab responses to the IgM and IgG3 isotypes, these responses are T-cell dependent. The ability of allografts to elicit weak anti-α1,3Gal but strong allo-Ab responses, can be explained by the dependence of α1,3Gal-specific B cells on cognate help from T cells. (C) 2000 Elsevier Science S.A. All rights reserved.
KW - Anti-α1,3gal antibodies
KW - Galactosyltransferase knock-out
KW - Humoral responses
KW - Mice
KW - Xenoantibodies
KW - Xenotransplantation
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U2 - 10.1016/S0966-3274(00)00017-4
DO - 10.1016/S0966-3274(00)00017-4
M3 - Article
C2 - 11005319
AN - SCOPUS:0033832480
SN - 0966-3274
VL - 8
SP - 129
EP - 137
JO - Transplant Immunology
JF - Transplant Immunology
IS - 2
ER -