title: CIN85 drives B cell responses by linking BCR signals to the canonical NF-kappaB pathway.
abstract: 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.
authors.affiliation: Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Turumi-ku, Kanagawa 230-0045, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kometani
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamada
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yokosuka
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.forename: Klaus
authors.initials: K
authors.lastname: Rajewsky
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ishiai
authors.forename: Masaki
authors.initials: M
authors.lastname: Hikida
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D001483:Base Sequence; D049109:Cell Proliferation; D002470:Cell Survival; D017931:DNA Primers / Q000235:genetics; D051550:I-kappa B Kinase / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D016328:NF-kappa B; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011947:Receptors, Antigen, B-Cell; C498782:Sh3kbp1 protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse