Kenny J J, Fischer R T, Lustig A, Dintzis H, Katsumata M, Reed J C, Longo D L
Biologic Carcinogenesis Development Program/Science Applications International Corporation-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA.
J Immunol. 1996 Aug 1;157(3):1054-61.
A point mutation in the pleckstrin homology domain of the mouse Bruton's tyrosine kinase (btk) gene results in an X-linked immune defect, Xid, characterized by immunologic unresponsiveness to polymeric carbohydrate Ags. In Xid mice, B cells specific for phosphocholine (PC) do not develop in peripheral lymphoid tissues because they either fail to be positively selected from the marrow or they are clonally deleted via an Ag-driven, receptor-mediated process. Overexpression of the bcl-2 gene allows PC-specific B cells to survive and mature in Xid mukappa anti-PC transgenic mice, but PC-specific B cells are not rescued by bcl-2 in Xid mu-only transgenic mice. The failure of bcl-2 to rescue PC-specific B cells, in mu-only transgenic mice suggests that either it does not correct the btk defect in the Ag-driven selection process that occurs in pre-B cells and/or in very immature B cells or that a btk-dependent proliferative phase is required for the selection and amplification of the PC-specific B cells in mu-only transgenic mice. The rescue of PC-specific B cells in mukappa transgenic mice indicates that bcl-2 can alter receptor-mediated B cell selection at late stages in B cell development. The rescued PC-specific B cells in Xid male mice do not exhibit an altered proliferation profile in response to B cell-stimulating agents compared with B cells from unmanipulated Xid mice; thus, they fail to respond to soluble anti-mu, or PC-dextran, but they proliferate in response to PC, anti-mu, or anti-id conjugated to Sepharose.
小鼠布鲁顿酪氨酸激酶（btk）基因的pleckstrin同源结构域中的一个点突变导致X连锁免疫缺陷Xid，其特征是对聚合碳水化合物抗原无免疫反应。在Xid小鼠中，对磷酸胆碱（PC）特异的B细胞在外周淋巴组织中无法发育，因为它们要么未能从骨髓中被阳性选择，要么通过抗原驱动的、受体介导的过程被克隆清除。bcl-2基因的过表达使PC特异的B细胞在Xid mukappa抗PC转基因小鼠中存活并成熟，但在仅Xid mu转基因小鼠中，PC特异的B细胞不能被bcl-2挽救。在仅mu转基因小鼠中，bcl-2未能挽救PC特异的B细胞，这表明要么它没有纠正前B细胞和/或非常不成熟的B细胞中发生的抗原驱动选择过程中的btk缺陷，要么在仅mu转基因小鼠中，PC特异的B细胞的选择和扩增需要一个btk依赖的增殖阶段。mukappa转基因小鼠中PC特异的B细胞的挽救表明bcl-2可以在B细胞发育的后期改变受体介导的B细胞选择。与未处理的Xid小鼠的B细胞相比，Xid雄性小鼠中挽救的PC特异的B细胞对B细胞刺激剂的增殖反应没有改变；因此，它们对可溶性抗μ或PC-葡聚糖无反应，但对与琼脂糖偶联的PC、抗μ或抗独特型有增殖反应。
