Résumé : FcγRIIB are single-chain low-affinity receptors for IgG that bear an immunoreceptor tyrosine-based inhibition motif (ITIM) in their intracytoplasmic domain and that negatively regulate immunoreceptor tyrosine-based activation motif (ITAM)-dependent cell activation. In B cells, coaggregation of the B cell receptor (BCR) and FcγRIIB leads to an inhibition of B cell activation. Inhibitory properties of FcγRIIB have been related to the recruitment of SHIP, an SH2 domain-containing inositol 5-phosphatase (referred to as SHIP1), via ITIM phosphorylated FcγRIIB. Here, we demonstrate that the second SH2 domain-containing inositol 5-phosphatase SHIP2 could also bind to the FcγRIIB ITIM. As a model, a FcγRIIB deficient B cell line (IIA1.6), transfected with a cDNA encoding either w.t. FcγRIIB1' or FcγRIIB1' whose ITIM tyrosine was mutated has been used. SHIP2 tyrosine phosphorylation and association to the adaptator protein Shc were only found in transfectants expressing w.t. FcγRIIB1'. SHIP2 was also found to bind to a phosphopeptide corresponding to the ITIM sequence of FcγRIIB. There was no binding to the nonphosphorylated peptide. Finally, both SHIP2 and SHIP1 were coprecipitated with FcγRIIB1' upon coaggregation with BCR in IIA1.6 transfectants. Copyright (C) 2000 Elsevier Science B.V.