Differential effects of injections of anti-mu and anti-delta monoclonal antibodies on B-cell populations in adult mice - Regulation of xenoreactive natural antibody-producing cells

Background. The depletion of differential B cell and xenoreactive natural a ntibodies (XNA) by anti-delta and anti-mu injections was analyzed in adult mice. Sequential treatment with anti-delta and then anti-mu induces a compl ete depletion of B cells and XNA and represents a potential approach to ind uce xenograft tolerance. Methods. Adult mice were injected with anti-mu, anti-delta, anti-delta then anti-mu, or control isotype monoclonal antibodies from day 0 to day 14. Th e different B-cell populations were analyzed by FACS and immunohistology, I g production was tested by ELISA. XNA were analyzed by FACS. Results. Anti-mu injections induced a depletion of IgM(high), immature B ce lls, marginal zone B cells, and B1 cells and an increase of IgG-XNA product ion. Anti-delta injections induced mature conventional IgD(high) B-cell dep letion and increased IgM-XNA production. Interestingly, sequential injectio ns of anti-delta then anti-mu induced a depletion of immature B cells, matu re B cells (MZ, B2, and B1), and XNA. Conclusions. These results demonstrate that mature B-cell depletion in adul t mice can be obtained by mAb injections and depends on the surface immunog lobulin cross-linking threshold. Indeed, anti-mu mAb depleted IgM(high) B c ells (MZ and B1) and anti-delta, IgDhigh B cells (B2). The differential B-c ell suppression shows that conventional B cells are responsible in the IgG- XNA production and MZ and B1 cells in the IgM-XNA production. Sequential re peated injections of anti-delta then anti-mu mAb depleted all B-cell popula tions and suppressed the whole XNA production.