B-Cell Suppression in Adult Mice Injected with Anti-δ Followed by Anti-μ mAb

Cross-linking of surface IgM or IgD B-cell receptors (BCR) with appropriate anti-Ig antibodies induces IgMhigh or IgDhigh B-cell depletion, respectively. The aim of this paper is to analyze how injections of anti-δ followed by anti-μ monoclonal antibodies (mAb) can deplete and suppress B cells and then induce T-independent type 2 antigen tolerance in adult mice even after treatment is stopped. The experimental protocol consisted of three daily injections of anti-δ mAb followed by repeated injections of anti-μ mAb. It shows that a sequential injection of anti-δ and anti-μ 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-δ mAb from the circulation, B cells reappear as an IgD+ IgM− B-cell population in the bone marrow (BM) and spleen. The origin of IgD+ IgM− cells was studied in scid mouse transfer models. We show that IgD+ IgM− B cells are not mature cells reexpressing sIgD but BM-derived cells that require a T-cell presence to be developed. The lack of sIgM expression by posttranscriptional regulation and the need of T-cell help for escaping anti-μ negative selection suggest strongly that this population had properties similar to those of anergized B cells. These results support the potential use of sequential injections of anti-δ and anti-μ in the prevention of xenograft rejection.