Protein-tyrosine phosphatase SHP-1 is dispensable for Fc gamma RIIB-mediated inhibition of B cell antigen receptor activation

The inhibitory Fe receptor, Fc gamma RIIB, provides a signal that aborts B cell antigen receptor activation, blocking extracellular calcium influx. Because the protein-tyrosine phosphatase SHP-1 binds tyrosy1 phosphorylated Fc gamma RIIB and Fc gamma RIIB-mediated inhibition is defective in motheaten (me/me) mice, which do not express SHP-1, it was proposed that SHP-1 mediates Fc gamma RIIB signaling in B cells (D'Ambrosio, D., Hippen, K. L., Minskoff S. A., Mellman, I., Pani, G., Siminovitch, K. A., and Cambier, J. C. (1995) Science 268, 293-297). However, SHP-1 is dispensable for Fc gamma RIIB-mediated inhibition of Fc epsilon RI signaling in mast cells (One, M., Bolland, S., Tempst, P., and Ravetch, J. V. (1996) Nature 383, 263-266), prompting us to re-examine the role of SHP-1 in Fc gamma RIIB signaling in B cells. We generated immortalized sIgM+, Fc gamma RIIB+ cell lines from me/me mice and normal littermates. Co-Ligation of Fc gamma RIIB and the sIgM antigen receptor inhibits calcium influx in both cell lines. Inhibition is reversed by preincubation with anti-Fc gamma RIIB antibodies, indicating that it is mediated bg Fc gamma RIIB. The inositol 5' phosphatase SHIP is recruited to tyrosyl-phosphorylated Fc gamma RIIB in both cell Lines, Fc gamma RIIB-mediated CD19 dephosphorylation also occurs in the presence or the absence of SHP-1, Our results establish that SHP-1 is dispensable for Fc gamma RIIB-mediated inhibition of sIgM antigen receptor signaling.