CIN85 is an adaptor known for its interaction with the E3 ubiquitin ligase Cbl; it has been proposed to function in endocytosis of membrane receptors. In the Journal of Experimental Medicine, Kometani et al. report that CIN85 links the B cell antigen receptor to activation of the canonical NF-κB pathway. B cell–specific deletion of CIN85 does not effect the induction of T cell–dependent antibody responses or germinal center formation. However, T cell–independent responses are almost entirely lost because of the defective survival and proliferation of mutant B cells after stimulation with antibodies to immunoglobulin M. CIN85 deficiency results in less activation of the kinase IKK complex, whereas activation of noncanonical NF-κB downstream of lipopolysaccharide, the costimulator CD40 and the activator BAFF remains intact. In addition, the development of B-1 cells is substantially impaired in CIN85-deficient mice, which further supports the idea that CIN85 is involved in signal transduction mediated via the B cell antigen receptor.

J. Exp. Med. 208, 1447–1457 (2011)