CIN85 drives B cell responses by linking BCR signals to the canonical NF-kappaB pathway.

Kohei Kometani, Takayuki Yamada, Yoshiteru Sasaki, Tadashi Yokosuka, Takashi Saito, Klaus Rajewsky, Masamichi Ishiai, Masaki Hikida, Tomohiro Kurosaki

Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Turumi-ku, Kanagawa 230-0045, Japan.

The Journal of experimental medicine 2011 Jul 4

filter terms:

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-β activation and cellular responses to B cell receptor (BCR) cross-linking in vitro. Introduction of a constitutively active IKK-β 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-β activation, thereby contributing to T cell-independent immune responses.

Citation

Kohei Kometani, Takayuki Yamada, Yoshiteru Sasaki, Tadashi Yokosuka, Takashi Saito, Klaus Rajewsky, Masamichi Ishiai, Masaki Hikida, Tomohiro Kurosaki. CIN85 drives B cell responses by linking BCR signals to the canonical NF-kappaB pathway. The Journal of experimental medicine. 2011 Jul 4;208(7):1447-57