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

[1]

Aicher A, 1999, J IMMUNOL, V163, P5786

[2] Molecular mechanisms of immunoglobulin E regulation [J].

Bacharier, LB ;

Jabara, H ;

Geha, RS .

INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY, 1998, 115 (04) :257-269

[3] THE CD40 ANTIGEN AND ITS LIGAND [J].

BANCHEREAU, J ;

BAZAN, F ;

BLANCHARD, D ;

BRIERE, F ;

GALIZZI, JP ;

VANKOOTEN, C ;

LIU, YJ ;

ROUSSET, F ;

SAELAND, S .

ANNUAL REVIEW OF IMMUNOLOGY, 1994, 12 :881-922

[4]

BERBERICH I, 1994, J IMMUNOL, V153, P4357

[5] CD40-DEFICIENT MICE GENERATED BY RECOMBINATION-ACTIVATING GENE-2-DEFICIENT BLASTOCYST COMPLEMENTATION [J].

CASTIGLI, E ;

ALT, FW ;

DAVIDSON, L ;

BOTTARO, A ;

MIZOGUCHI, E ;

BHAN, AK ;

GEHA, RS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (25) :12135-12139

[6] CD40 expression and function in murine B cell ontogeny [J].

Castigli, E ;

Young, F ;

Carossino, AM ;

Alt, FW ;

Geha, RS .

INTERNATIONAL IMMUNOLOGY, 1996, 8 (03) :405-411

[7]

Chang T M, 1995, Biotechnol Annu Rev, V1, P267

[8] QUANTITATION OF IMMUNOGLOBULIN MU-GAMMA-1 HEAVY-CHAIN SWITCH REGION RECOMBINATION BY A DIGESTION CIRCULARIZATION POLYMERASE CHAIN-REACTION METHOD [J].

CHU, CC ;

PAUL, WE ;

MAX, EE .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (15) :6978-6982

[9] Cooperation of multiple signaling pathways in CD40-regulated gene expression in B lymphocytes [J].

Dadgostar, H ;

Zarnegar, B ;

Hoffmann, A ;

Qin, XF ;

Truong, U ;

Rao, G ;

Baltimore, D ;

Cheng, GH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (03) :1497-1502

[10] X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-κB signaling [J].

Döffinger, R ;

Smahi, A ;

Bessia, C ;

Geissmann, F ;

Feinberg, J ;

Durandy, A ;

Bodemer, C ;

Kenwrick, S ;

Dupuis-Girod, S ;

Blanche, S ;

Wood, P ;

Rabia, SH ;

Headon, DJ ;

Overbeek, PA ;

Le Deist, F ;

Holland, SM ;

Belani, K ;

Kumararatne, DS ;

Fischer, A ;

Shapiro, R ;

Conley, ME ;

Reimund, E ;

Kalhoff, H ;

Abinun, M ;

Munnich, A ;

Israël, A ;

Courtois, G ;

Casanova, JL .

NATURE GENETICS, 2001, 27 (03) :277-285

← 1 2 3 4 5 6 →