LIME acts as a transmembrane adapter mediating BCR-dependent B-cell activation

Abstract

Assembly of a signaling complex around the transmembrane adapter LAT is essential for the transmission of T-cell receptor (TCR)-mediated signaling. However, a LAT-like molecule responsible for the initial activation events in B-cell receptor (BCR) signaling has not yet been identified. Here, we show that LIME is a transmembrane adaptor required for BCR-mediated B-cell activation. LIME was found to be expressed in mouse splenic B cells. Upon BCR cross-linking, LIME was tyrosine phosphorylated by Lyn and associated with Lyn, Grb2, PLC-γ2, and PI3K. Reduction of LIME expression by the introduction of siRNA resulted in the disruption of BCR-mediated activation of MAPK, calcium flux, NF-AT, PI3K, and NF-κB. Taken together, these results establish that LIME is an essential transmembrane adaptor linking BCR ligation to the downstream signaling events that lead to B-cell activation.