TY - JOUR
T1 - Negative regulation of CD40-mediated B cell responses by E3 ubiquitin ligase Casitas-B-lineage lymphoma protein-B
AU - Qiao, Guilin
AU - Lei, Minxiang
AU - Li, Zhenping
AU - Sun, Yonglian
AU - Minto, Andrew
AU - Fu, Yang Xin
AU - Ying, Haiyan
AU - Quigg, Richard J.
AU - Zhang, Jian
PY - 2007/10/1
Y1 - 2007/10/1
N2 - It has been documented that CD40 is essential for B cell function. Casitas-B-lineage lymphoma protein-b (Cbl-b), an adapter protein and ubiquitin ligase, has been shown to regulate the activation of T and B cells through their Ag receptors. In this study, we report that CD40-induced B cell proliferation is significantly augmented in mice lacking Cbl-b. Furthermore, Cbl-b -/- mice display enhanced thymus-dependent Ab responses and germinal center formation, whereas introduction of CD40 deficiency abolishes these effects. Hyper thymus-dependent humoral response in Cbl-b-/- mice is in part due to an intrinsic defect in B cells. Mechanistically, Cbl-b selectively down-modulates CD40-induced activation of NF-κB and JNK. Cbl-b associates with TNF receptor-associated factor 2 upon CD40 ligation, and inhibits the recruitment of TNF receptor-associated factor 2 to the CD40. Together, our data suggest that Cbl-b attenuates CD40-mediated NF-κB and JNK activation, thereby suppressing B cell responses.
AB - It has been documented that CD40 is essential for B cell function. Casitas-B-lineage lymphoma protein-b (Cbl-b), an adapter protein and ubiquitin ligase, has been shown to regulate the activation of T and B cells through their Ag receptors. In this study, we report that CD40-induced B cell proliferation is significantly augmented in mice lacking Cbl-b. Furthermore, Cbl-b -/- mice display enhanced thymus-dependent Ab responses and germinal center formation, whereas introduction of CD40 deficiency abolishes these effects. Hyper thymus-dependent humoral response in Cbl-b-/- mice is in part due to an intrinsic defect in B cells. Mechanistically, Cbl-b selectively down-modulates CD40-induced activation of NF-κB and JNK. Cbl-b associates with TNF receptor-associated factor 2 upon CD40 ligation, and inhibits the recruitment of TNF receptor-associated factor 2 to the CD40. Together, our data suggest that Cbl-b attenuates CD40-mediated NF-κB and JNK activation, thereby suppressing B cell responses.
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U2 - 10.4049/jimmunol.179.7.4473
DO - 10.4049/jimmunol.179.7.4473
M3 - Article
C2 - 17878343
AN - SCOPUS:59849117647
SN - 0022-1767
VL - 179
SP - 4473
EP - 4479
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -