Submitted April 10, 2007
Accepted August 19, 2007
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
Toshimitsu Irei, Hideki Ohdan*, Wendy Zhou, Kohei Ishiyama, Yuka Tanaka, Kentaro Ide, and Toshimasa Asahara
Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
* Corresponding author; email: hohdan{at}hiroshima-u.ac.jp.
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 (GalNAc
1-3,Fuc1-2Gal) conjugated to bovin serum albumin (BSA) (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.
