Reconstitution of B cell function in murine models of immunodeficiency

Murine models of immunodeficiency were used to evaluate strategies that might allow B cell engraftment in patients with X-linked agammaglobulinemia. Mice with defects in Btk or μ heavy chain were given 2.5 × 106 bone marrow cells from wild-type congenic donors. In the absence of any preparative regimen or immunosuppression, Btk-deficient mice on the CBA background developed normal concentrations of serum IgM and IgG3 by 12 weeks posttransplant. By contrast, μ heavy chain-deficient mice on the C57BL/6 background required some immunosuppression to achieve engraftment. Treatment of these mice with anti-T-cell antibodies 2 and 4 days prior to transplant resulted in normal concentrations of serum immunoglobulins by 6 weeks posttransplant. These pretreated mice had only 10% of the normal number of splenic B cells and they had no evidence of donor T cell engraftment. These results suggest that myelotoxic drugs may not be needed to achieve B cell engraftment in B-cell-deficient subjects.