THE CD40 LIGAND, GP39, IS DEFECTIVE IN ACTIVATED T-CELLS FROM PATIENTS WITH X-LINKED HYPER-IGM SYNDROME

被引：764

作者：

ARUFFO, A

FARRINGTON, M

HOLLENBAUGH, D

LI, X

MILATOVICH, A

NONOYAMA, S

BAJORATH, J

GROSMAIRE, LS

STENKAMP, R

NEUBAUER, M

ROBERTS, RL

NOELLE, RJ

LEDBETTER, JA

FRANCKE, U

OCHS, HD

机构：

[1] UNIV WASHINGTON, SCH MED, DEPT PEDIAT, SEATTLE, WA 98195 USA

[2] UNIV WASHINGTON, SCH MED, DEPT BIOL STRUCT, SEATTLE, WA 98195 USA

[3] STANFORD UNIV, MED CTR, DEPT GENET, STANFORD, CA 94305 USA

[4] STANFORD UNIV, MED CTR, HOWARD HUGHES MED INST, STANFORD, CA 94305 USA

[5] UNIV CALIF LOS ANGELES, MED CTR, DEPT PEDIAT, LOS ANGELES, CA 90024 USA

[6] DARTMOUTH COLL, SCH MED, DEPT MICROBIOL, LEBANON, NH 03756 USA

来源：

CELL | 1993年 / 72卷 / 02期

关键词：

D O I：

10.1016/0092-8674(93)90668-G

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The prominent role of the CD40 receptor in B cell responses led us to investigate the role of the gp39-CD40 interaction in a group of primary immunodeficient patients with defective antibody production. Here we report that patients with hyper-IgM syndrome (HIM) have a defective gp39-CD40 interaction. B cells from HIM patients express functional CD40, but their T cells do not bind CD40-Ig. These patients expressed normal levels of gp39 mRNA, but these mRNAs encode defective gp39 proteins owing to mutations in the extracellular domain of gp39. Soluble recombinant forms of gp39 containing these mutations were unable to bind CD40 and drive normal B cell proliferation. The gene encoding gp39 was mapped to Xq26, the X chromosome region where the gene responsible for HIM had previously been mapped. These data suggest that a defect in gp39 is the basis of X-linked HIM.

引用

页码：291 / 300

页数：10

共 47 条

[1] MOLECULAR AND BIOLOGICAL CHARACTERIZATION OF A MURINE LIGAND FOR CD40 [J].