DEFECTIVE EXPRESSION OF T-CELL CD40 LIGAND CAUSES X-LINKED IMMUNODEFICIENCY WITH HYPER-IGM
DEFECTIVE EXPRESSION OF T-CELL CD40 LIGAND CAUSES X-LINKED IMMUNODEFICIENCY WITH HYPER-IGM
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DOI：
10.1038/361539a0
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发表时间：
1993-02-11
期刊：
影响因子：
64.8
通讯作者：
KROCZEK, RA
中科院分区：
文献类型：
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作者：
KORTHAUER, U;GRAF, D;KROCZEK, RA
X染色体连锁免疫缺陷伴高IgM（HIGM 1，MIM编号308230）是一种罕见疾病，其特征为反复细菌感染，IgG、伊加和IgE极低或缺失，IgM和IgD血清水平正常至升高1 -3。已经表明，HIGM 1是由T细胞对B细胞的无效帮助引起的4。我们和其他人5 -8已经确定了一种新的，TNF相关的激活蛋白（TRAP），它只在刺激的T细胞表面表达6，8。TRAP是M（r）33，000的II型跨膜蛋白，是CD 40的生理配体（参考文献5-8）。在淋巴因子存在下，B细胞上的CD 40交联诱导免疫球蛋白类别从IgM转换为IgG、伊加或IgE 5，9-11。TRAP基因定位于X染色体q26.3-q27.1（参考文献6），表明与先前被指定为Xq 26（参考文献12-14）的HIGM 1存在因果关系。在这里，我们提出的证据表明，在TRAP基因的点突变引起的非功能性或缺陷的TRAP表达的患者的T细胞表面的HIGM 1。TRAP与功能完整的B细胞上的CD 40相互作用的结果失败是在HIGH M1中观察到的免疫球蛋白同种型缺陷的原因。
X CHROMOSOME-LINKED immunodeficiency with hyper-IgM (HIGM1, MIM number 308230) is a rare disorder characterized by recurrent bacterial infections, very low or absent IgG, IgA and IgE, and normal to increased IgM and IgD serum levels1-3. HIGM1 has been suggested to result from ineffective T-cell help for B cells4. We and others5-8 have identified a novel, TNF-related activation protein (TRAP) that is exclusively expressed on the surface of stimulated T cells6,8. TRAP, a type II transmembrane protein of M(r) 33,000, is the physiological ligand for CD40 (refs 5-8). Crosslinking of CD40 on B cells induces, in the presence of lymphokines, immunoglobulin class switching from IgM to IgG, IgA or IgE5,9-11. Mapping of the TRAP gene to the X-chromosomal location q26.3-q27.1 (ref. 6) suggested a causal relationship to HIGM1, which had previously been assigned to Xq26 (refs 12-14). Here we present evidence that point mutations in the TRAP gene give rise to nonfunctional or defective expression of TRAP on the surface of T cells in patients with HIGM1. The resultant failure of TRAP to interact with CD40 on functionally intact B cells is responsible for the observed immunoglobulin isotype defect in HIGM1.