Ochs H D, Aruffo A
Department of Pediatrics, University of Washington School of Medicine, Seattle 98195.
Curr Opin Pediatr. 1993 Dec;5(6):684-91. doi: 10.1097/00008480-199312000-00008.
The molecular basis for three well-defined X-linked diseases has recently been identified. In X-linked agammaglobulinemia, the gene encoding a novel cytoplasmic tyrosine kinase (btk) expressed by B cells is defective. This B-cell-specific kinase belongs to a new subfamily of tyrosine kinases. The molecular defect in X-linked hyper IgM affects the gene encoding the CD40 ligand (CD40L, gp39) on T cells. This protein binds to its natural receptor, CD40, expressed constitutively by B cells. The ligand-receptor interaction initiates B-cell proliferation and isotype switching. The molecular defect in X-linked severe combined immunodeficiency disease has been assigned to the gene encoding the gamma chain of the interleukin-2 receptor (IL-2R gamma), which is constitutively expressed by T cells and is involved in the formation of high and intermediate affinity IL-2R complexes. IL-2R-gamma is responsible for the failure of X-linked severe combined immunodeficiency disease T and B lymphocytes to respond to IL-2-dependent signals.
最近已确定了三种明确的X连锁疾病的分子基础。在X连锁无丙种球蛋白血症中，B细胞表达的一种新型细胞质酪氨酸激酶（btk）的编码基因存在缺陷。这种B细胞特异性激酶属于酪氨酸激酶的一个新亚家族。X连锁高IgM血症中的分子缺陷影响T细胞上编码CD40配体（CD40L，gp39）的基因。该蛋白与其天然受体CD40结合，CD40由B细胞组成性表达。配体-受体相互作用启动B细胞增殖和同种型转换。X连锁严重联合免疫缺陷病中的分子缺陷已归因于编码白细胞介素-2受体（IL-2Rγ）γ链的基因，该基因由T细胞组成性表达，并参与高亲和力和中等亲和力IL-2R复合物的形成。IL-2R-γ导致X连锁严重联合免疫缺陷病的T和B淋巴细胞无法对IL-2依赖性信号作出反应。
