Human Fc receptor-like 5 interacts with key signaling proteins in B cells (P1116)

• Published in: The Journal of immunology (1950) Vol. 190; no. 1_Supplement; pp. 64 - 64.5
• Main Authors: Franco, Andrea, Damdinsuren, Bazarragchaa, Dement-Brown, Jessica, Li, Huifang, Tolnay, Mate
• Format: Journal Article
• Language: English
• Published: 01-05-2013
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.190.Supp.64.5

Abstract
B cell response is modulated by an array of co-receptors which transduce activating and/or inhibitory signals. The balance of these stimuli will determine cell function and fate. Human Fc receptor-like 5 (FCRL5) is a transmembrane protein containing immunoglobulin superfamily domains and is expressed by distinct subsets of B cells. The functional role of FCRL5 is poorly understood. However FCRL5 has been reported to be upregulated in several B cell tumors, including hairy cell leukemia, mantle cell lymphoma and multiple myeloma. The cytoplasmic tail of FCRL5 has two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and one predicted imunoreceptor tyrosine-based activation motif (ITAM). Both ITIMs were shown to interact with the protein phosphatase SHP-1 upon co-ligation of the B cell antigen receptor (BCR) and FCRL5, inhibiting calcium mobilization and tyrosine phosphorylation. Using Rec-1 FCRL5-positive cells and Daudi cells which have been transfected to stably express FCRL5, we investigated signaling components and pathways engaged upon FCRL5 stimulation. We found that FCRL5 forms protein complexes with phospholipase C (PLC) gamma 2 and CD19. CD19 is a well established positive regulator of BCR signaling, whereas PLC gamma 2 is critical for calcium flux in B cells. Therefore our findings could be part of the mechanism by which FCRL5 regulates B cell activation through signal transduction and calcium mobilization.