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CIN85 drives B cell responses by linking BCR signals to the canonical NF- kB pathway. (Tomohiro Kurosaki in JEM)

CIN85, an adaptor protein which binds the C-terminal domain of tyrosine phosphorylated Cbl and Cbl-b, has been thought to be involved in the internalization and subsequent degradation of receptors. However, its physiological function remains unclear. To determine its role in B cells, we used Mb1-cre to generate mice with a B cell-specific deletion of CIN85. These mice had impaired T cell-independent type II antibody responses in vivo and diminished IKK-beta activation and cellular responses to B cell receptor (BCR) cross-linking in vitro. Introduction of a constitutively active IKK-beta construct corrected the defective antibody responses as well as cellular responses in the mutant mice. Together, our results suggest that CIN85 links the BCR to IKK-beta activation, thereby contributing to T cell- independent immune responses.



Tomohiro Kurosaki
Immunology Frontier Research Center (IFReC), Osaka University