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Reconstitution of B cell function in murine models of immunodeficiency.

机译:免疫缺陷小鼠模型中B细胞功能的重建。

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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 mu heavy chain were given 2.5 x 10(6) 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, mu 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.
机译:免疫缺陷的小鼠模型被用于评估可能允许X连锁无球蛋白血症患者B细胞移植的策略。在Btk或mu重链中有缺陷的小鼠接受了来自野生型同基因供体的2.5 x 10(6)骨髓细胞。在没有任何准备方案或免疫抑制的情况下,CBA背景上的Btk缺陷型小鼠在移植后12周时可产生正常浓度的血清IgM和IgG3。相比之下,在C57BL / 6背景上的mu重链缺陷小鼠需要一定的免疫抑制以实现植入。移植前2天和4天用抗T细胞抗体治疗这些小鼠,导致移植后6周血清免疫球蛋白浓度达到正常水平。这些经过预处理的小鼠仅具有正常脾脏B细胞数量的10%,并且没有供体T细胞植入的证据。这些结果表明,在缺乏B细胞的受试者中可能不需要骨髓毒性药物来实现B细胞植入。

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