The role of antibodies in liver graft-induced tolerance in mice: passive transfer of serum and effect of recipient B-cell depletion.

MOUSE liver allografts are spontaneously accepted , _ . without immunosuppression and induce donor-spe'c:ific acceptance of subsequently transplanted skin or heart allografts 1 despite various degrees of MHC incompatibility. ; This in vivo tolerance is associated with donor-specific ~ reactivity in vitro, a phenomenon called "split tolerance."2 tTherefore. clonal deletion is unlikely to be the explanation !'of graft acceptance in this model. The same phenomenon3b has been observed in some rat .strain combinations. In the DA into PVG strain comb ina• 'lion, the liver is spontaneously accepted.3 whereas other · organs. such as kidney. heart. or skin. are rapidly rejected. A liver allograft in the rat is able to overcome the effects of · priming by donor antigen and to convert a state of immunological memory into one of specific transplantation tol, crance as demonstrated by reversal of ongoing heart and/or , akingraft rejection. 1.4 In the rat model. liver graft-induced · tolerance (LGT) has been attributed to cellular factors. , IUch as selective clonal deletion.79 and development of " IUppressor cells. 1O 12 as well as humoral factors. One popular explanation for these findings is the release of , , IOluble donor class I antigen by the liver allograft. which in aeparate experiments has been shown to prolong modestly allograft survival upon passive transfer. 1315 Antidonor class II antibodies were shown to exert an even more -powerful effect. 16 18 In this study, we tested the role of antibodies in LGT in the mouse model by analysing the biological activity of aerum from liver-grafted mice (> 100 days) and compared it to sera from heart and skin graft recipients using in vivo (serum transfer) and in vitro (MLR and CML) assays.