The persistent elimination of B cells responding to blood group A carbohydrates by synthetic group A carbohydrates and B-1 cell differentiation blockade: novel concept in preventing antibody-mediated rejection in ABO-incompatible transplantation.
We demonstrated a novel strategy for specific and persistent inhibition of antibody (Ab) production against blood group A or B carbohydrate determinants necessary for successful ABO-incompatible transplantation. Similar to human blood group O or B individuals, mice have naturally occurring Abs against human blood group A carbohydrates in their sera. B cells with receptors for A carbohydrates in mice belonging to the CD5(+)CD11b(+)B-1a subset have phenotypic properties similar to those of human B cells. These cells could be temporarily eliminated by injecting synthetic A carbohydrates (GalNAcalpha1-3, Fucalpha1-2Gal) conjugated to bovine serum albumin (A-BSA) and anti-BSA Abs. In mice that received the injection of A-BSA/anti-BSA Abs, the serum levels of anti-A IgM were reduced, but immunization with human A erythrocytes resulted in increased serum levels of anti-A Abs. When combined with cyclosporin A (CsA) treatment, which blocks B-1a cell differentiation, and treatment with A-BSA/anti-BSA Abs, the serum levels of anti-A Abs were persistently undetectable in the mice even after the immunization. B cells with receptors for A carbohydrates were markedly reduced in these mice. These results are consistent with the hypotheses that treatment with A-BSA/anti-BSA Abs temporarily depletes B cells responding to A determinants, and CsA treatment prevents the replenishment of these cells.
Irei
Toshimitsu
T
Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Ohdan
Hideki
H
Zhou
Wendy
W
Ishiyama
Kohei
K
Tanaka
Yuka
Y
Ide
Kentaro
K
Asahara
Toshimasa
T
D000017:ABO Blood-Group System; D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016572:Cyclosporine / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods*; D051379:Mice; D009844:Oligosaccharides / Q000737:chemistry / Q000276:immunology*; D025942:Oligosaccharides, Branched-Chain; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use
D000017:ABO Blood-Group System; D000906:Antibodies; D009844:Oligosaccharides; D025942:Oligosaccharides, Branched-Chain; C101335:blood group A trisaccharide; D012710:Serum Albumin, Bovine; D016572:Cyclosporine