title: Postnatal xenogeneic B-cell tolerance in swine following in utero intraportal antigen exposure.
abstract: BACKGROUND
  The objective of this study was to investigate the humoral immune response to xenogeneic antigens administered during the fetal state utilizing a baboon-to-pig model.
  
  
  METHODS
  Nine fetuses from an alpha-1,3-galactosyltransferase gene knockout (GalT-KO) MGH-miniature swine sow underwent transuterine ultrasound-guided intraportal injection of T-cell depleted baboon bone marrow (B-BM) at mid-gestation. Two juvenile GalT-KO swine undergoing direct B-BM intraportal injection were used as controls.
  
  
  RESULTS
  Postnatal humoral tolerance was induced in the long-term surviving piglets as demonstrated by the absence of any antibody response to baboon donor cells. In addition, a second intraportal B-BM administration at 2.5 months post-birth led to no antibody formation despite re-exposure to xenogeneic antigens. This B-cell unresponsiveness was abrogated only when the animal was exposed subcutaneously to third-party xenogeneic and allogeneic antigens, suggesting that the previously achieved humoral non-responsiveness was donor specific. In comparison, the two juvenile GalT-KO control swine demonstrated increasing anti-baboon IgM and IgG levels following intraportal injection.
  
  
  CONCLUSIONS
  In summary, xenogeneic B-cell tolerance was induced through in utero intraportal exposure to donor cells and this tolerance persisted following postnatal rechallenge with donor B-BM, but was lost on exposure to third-party antigen, possibly as a result of cross-reactive antibody formation.
authors: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors: Nalu
authors: N
authors: Navarro Alvarez
authors: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors: Alexander
authors: A
authors: Zhu
authors: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors: Ronald S
authors: RS
authors: Arellano
authors: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors: Mark A
authors: MA
authors: Randolph
authors: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors: Michael
authors: M
authors: Duggan
authors: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors: John
authors: J
authors: Scott Arn
authors: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors: Christene A
authors: CA
authors: Huang
authors: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors: David H
authors: DH
authors: Sachs
authors: Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors: Parsia A
authors: PA
authors: Vagefi
mesh_terms: D000818:Animals; D000910:Antibodies, Heterophile / Q000276:immunology; D015478:Antigens, Heterophile / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D005260:Female; D007108:Immune Tolerance; D056724:Immunity, Humoral; D010215:Papio / Q000276:immunology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology; D013552:Swine / Q000276:immunology*; D014183:Transplantation, Heterologous / Q000379:methods*
chemical_list: D000910:Antibodies, Heterophile; D015478:Antigens, Heterophile
keywords: B-cell tolerance; in utero tolerance; xenotransplant