B-Cell suppression in adult mice injected with anti-delta followed by anti-mu mAb

Cross-linking of surface IgM or IgD B-cell receptors (BCR) with appropriate anti-Ig antibodies induces IgM(high) or IgD(high) B-cell depletion, respec tively. The aim of this paper is to analyze how injections of anti-delta fo llowed by anti-mu monoclonal antibodies (mAb) can deplete and suppress B ce lls and then induce T-independent type 2 antigen tolerance in adult mice ev en after treatment is stopped. The experimental protocol consisted of three daily injections of anti-6 mAb followed by repeated injections of anti-p m Ab. It shows that a sequential injection of anti-6 and anti-mu mAb induces B-cell depletion and T-independent type 2 response downregulation. Morever, the T-dependent response is maintained, except for the IgG3 isotype. After clearance of the anti-6 mAb from the circulation, B cells reappear as an I gD(+) IgM(-) B-cell population in the bone marrow (BM) and spleen. The orig in of IgD(+) IgM(-) cells was studied in scid mouse transfer models. We sho w that IgD(+) IgM- B cells are not mature cells reexpressing sIgD but BM-de rived cells that require a T-cell presence to be developed. The lack of sIg M expression by posttranscriptional regulation and the need of T-cell help for escaping anti-mu negative selection suggest strongly that this populati on had properties similar to those of anergized B cells. These results supp ort the potential use of sequential injections of anti-delta and anti-mu in the prevention of xenograft rejection. (C) 2000 Academic Press.