title: Production of anti-ABO blood group antibodies after minor ABO-incompatible bone marrow transplantation in NOD/SCID/gamma(c)(null) mice.
abstract: ABO incompatibility is a barrier for solid organ transplantation, but not for hematopoietic stem cell transplantation. To investigate tolerance induction, we enrolled patients who had undergone minor ABO-incompatible (O into A group, n = 6) and ABO-identical (O into O group, n = 4) bone marrow transplantation (BMT). None of the six O into A patients were positive for recipient-specific (anti-blood group A) isohemagglutinins, whereas all four O into O patients were. Peripheral blood mononuclear cells (PBMCs) were engrafted into NOD/SCID/gamma(c)(null) (NOG) mice, followed by sensitization of blood group A red blood cells. Anti-blood group A antibodies (Abs) in the sera of the patients and the human PBMC-engrafted NOG mice were measured by enzyme-linked immunosorbent assays. Anti-blood group A Abs in the patients' sera were significantly correlated with anti-A isohemagglutinin titers (p < 0.01). In the human PBMC-engrafted NOG mice, anti-blood group A Abs were significantly lower in the O into A group than in the O into O group (p < 0.05), despite ex vivo restimulation of B cells. The results of this study suggest that long after receiving minor ABO-incompatible BMT, B cells derived from newly engrafted donor precursor cells were induced tolerance to recipient-specific antigens.
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tomita
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Fuchimoto
authors.forename: Takehiko
authors.initials: T
authors.lastname: Mori
authors.forename: Jun
authors.initials: J
authors.lastname: Kato
authors.forename: Tomoe
authors.initials: T
authors.lastname: Uemura
authors.forename: Makoto
authors.initials: M
authors.lastname: Handa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tazawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohdan
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kuroda
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D001787:Blood Group Incompatibility / Q000276:immunology*; D016026:Bone Marrow Transplantation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000097:blood; D053631:Interleukin Receptor Common gamma Subunit / Q000276:immunology; D007518:Isoantibodies / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged
chemical_list: D000017:ABO Blood-Group System; D007132:Immunoglobulin Isotypes; D053631:Interleukin Receptor Common gamma Subunit; D007518:Isoantibodies
keywords: B-cell tolerance; NOD/SCID/gamma(c)(null) mice; anti-ABO blood group antibodies; isohemagglutinins; minor ABO-incompatible bone marrow transplantation