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  • Title: Donor resting B cells induce indefinite prolongation of fully allogeneic cardiac grafts when delivered with anti-immunoglobulin-D monoclonal antibody: evidence for tolerogenicity of donor resting B cells in vivo.
    Author: Niimi M, Hara M, Witzke O, Morris PJ, Wood KJ.
    Journal: Transplantation; 1998 Dec 27; 66(12):1786-92. PubMed ID: 9884277.
    Abstract:
    BACKGROUND: Resting B (rB) cells have been shown to induce T-cell anergy in vitro and to prolong the survival of skin and cardiac grafts mismatched for minor histocompatibility antigens. However, rB cells were unable to modulate the rejection response when grafts mismatched for major histocompatibility complex antigens were transplanted. We reasoned that donor antigens, which presented via the indirect pathway by recipient antigen-presenting cells, in particular B cells, might influence the ability of rB cells to induce unresponsiveness. To explore this hypothesis, we used an anti-immunoglobulin (Ig)-D monoclonal antibody (mAb) specific for recipient B cells to deplete these cells, thereby decreasing the potential for indirect presentation in vivo. METHODS: CBA mice were pretreated with 1 x 10(7) donor rB or activated B (aB) cells 7 days before transplantation of a C57BL/10 cardiac graft in the absence or presence of anti-IgD mAb. RESULTS: Naive CBA mice rejected C57BL/10 grafts acutely (median survival time [MST]=8 days). Pretreatment with rB cells alone resulted in a modest prolongation of graft survival (MST=11.5 days). In marked contrast, when rB cells were delivered with anti-IgD mAb, indefinite graft prolongation (MST>100 days) was observed in all recipients. Interestingly, aB cells produced only a small prolongation of graft survival when delivered with anti-IgD mAb (MST=15 days). Recipients treated with anti-IgD mAb alone rejected C57BL/10 cardiac allografts acutely (MST=8 days). CONCLUSION: These data suggest that depletion of recipient B cells in vivo can augment the ability of donor rB cells to induce indefinite prolongation of fully allogeneic cardiac grafts. Thus, IgD+ B cells in the recipient may influence the development of unresponsiveness in vivo.
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