Journal
JOURNAL OF IMMUNOLOGY
Volume 179, Issue 7, Pages 4473-4479Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.179.7.4473
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Funding
- NIAMS NIH HHS [R01AR049775, K02 AR049047] Funding Source: Medline
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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 Immoral 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-kappa B 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-kappa B and JNK activation, thereby suppressing B cell responses.
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