TY - JOUR
T1 - The Binding Site for TRAF2 and TRAF3 but Not for TRAF6 Is Essential for CD40-Mediated Immunoglobulin Class Switching
AU - Jabara, Haifa H.
AU - Laouini, Dhafer
AU - Tsitsikov, Erdyni
AU - Mizoguchi, Emiko
AU - Bhan, Atul K.
AU - Castigli, Emanuela
AU - Dedeoglu, Fatma
AU - Pivniouk, Vadim
AU - Brodeur, Scott R.
AU - Geha, Raif S.
N1 - Funding Information:
We thank Dr. Genhong Cheng (UCLA) for his gift of mTRAF6 plasmid and T. Sannikova and A. Flint for excellent technical assistance. This work was supported by USPHS grant AI31136 and by a generous gift from Mr. N. Wallace.
PY - 2002/9/1
Y1 - 2002/9/1
N2 - 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 (CD40ΔTRAF6), TRAF2 and TRAF3 (CD40ΔTRAF2/3), or both (CD40ΔTRAFs) into B cells of CD40-/- mice. The in vivo isotype switch defect in CD40-/- mice was fully corrected by WT and CD40ΔTRAF6, partially by CD40ΔTRAF2/3, and not at all by CD40ΔTRAFs transgenes. CD40-mediated isotype switching, proliferation, and activation of p38, JNK, and NFκB in B cells were normal in WT and CD40ΔTRAF6 mice, severely impaired in CD40ΔTRAF2/3, and absent in CD40ΔTRAFs 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.
AB - 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 (CD40ΔTRAF6), TRAF2 and TRAF3 (CD40ΔTRAF2/3), or both (CD40ΔTRAFs) into B cells of CD40-/- mice. The in vivo isotype switch defect in CD40-/- mice was fully corrected by WT and CD40ΔTRAF6, partially by CD40ΔTRAF2/3, and not at all by CD40ΔTRAFs transgenes. CD40-mediated isotype switching, proliferation, and activation of p38, JNK, and NFκB in B cells were normal in WT and CD40ΔTRAF6 mice, severely impaired in CD40ΔTRAF2/3, and absent in CD40ΔTRAFs 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.
UR - https://www.scopus.com/pages/publications/18644383624
UR - https://www.scopus.com/pages/publications/18644383624#tab=citedBy
U2 - 10.1016/S1074-7613(02)00394-1
DO - 10.1016/S1074-7613(02)00394-1
M3 - Article
C2 - 12354380
AN - SCOPUS:18644383624
SN - 1074-7613
VL - 17
SP - 265
EP - 276
JO - Immunity
JF - Immunity
IS - 3
ER -