The binding site for TRAF2 and TRAF3 but not for TRAF6 is essential for CD40-mediated immunoglobulin class switching

被引：107

作者：

Jabara, HH

Laouini, D

Tsitsikov, E

Mizoguchi, E

Bhan, AK

Castigli, E

Dedeoglu, F

Pivniouk, V

Brodeur, SR

Geha, RS ^{[1
]}

机构：

[1] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

[3] Massachusetts Gen Hosp, Immunopathol Unit, Boston, MA 02115 USA

来源：

IMMUNITY | 2002年 / 17卷 / 03期

关键词：

D O I：

10.1016/S1074-7613(02)00394-1

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

To define the role of TRAF proteins in CD40-dependent isotype switching in B cells, we introduced wild-type (WT) and mutant CD40 transgenes that lacked the binding motifs for TRAF6 (CD40DeltaTRAF6), TRAF2 and TRAF3 (CD40DeltaTRAF2/3), or both (CD40DeltaTRAFs) into B cells of CD40(-/-) mice. The in vivo isotype switch defect in CD40(-/-) mice was fully corrected by WT and CD40Delta TRAF6, partially by CD40DeltaTRAF2/3, and not at all by CD40DeltaTRAFs transgenes. CD40-mediated isotype switching, proliferation, and activation of p38, JNK, and NFkappaB in B cells were normal in WT and CD40DeltaTRAF6 mice, severely impaired in CD40DeltaTRAF2/3, and absent in CD40DeltaTRAFs mice. These results suggest that binding to TRAF2 and/or TRAF3 but not TRAF6 is essential for CD40 isotype switching and activation in B cells.

引用

页码：265 / 276

页数：12

共 53 条

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