PMID: 22553780May 4, 2012Paper

Antibodies against growth factor receptors can inhibit the proliferation of transformed cells via a cis-interaction with inhibitory FcR

Immunology Letters
Odile Malbec, Marc Daëron

Abstract

When dimerized by Stem Cell Factor (SCF), the Receptor Tyrosine Kinase Kit triggers the proliferation of hematopoietic progenitors, including pro-B cells, and of some differentiated cells, including mast cells. We found previously that anti-Kit antibodies can mimic SCF and that anti-Kit-induced mast cell proliferation can be inhibited by the low-affinity IgG receptors FcγRIIB, when the two receptors are co-aggregated by IgG immune complexes. We show here that the same immune complexes inhibited anti-Kit-induced proliferation of Ba/F3 pro-B cells expressing wt Kit and FcγRIIB and that inhibition required the intracytoplasmic domain of FcγRIIB. Constitutively active Kit mutants are oncogenic. We show that Kit-dependent, ligand-independent proliferation of Ba/F3 cells expressing a constitutively dimerized Kit mutant was also inhibited by IgG immune complexes via FcγRIIB. FcγRIIB-dependent negative regulation therefore also affects Kit-dependent proliferation of transformed cells. Interestingly, the co-aggregation of Kit with FcγRIIB by immune complexes containing SCF also inhibited both growth factor-dependent and growth factor-independent proliferation of Ba/F3 cells expressing wt or mutated Kit, respectively. These results provi...Continue Reading

References

Jan 1, 1990·Annals of the New York Academy of Sciences·P DubreuilA Bernstein
Jul 1, 1991·The Journal of Experimental Medicine·M OgawaS Nishikawa
May 22, 2001·The Journal of Biological Chemistry·O MalbecM Daëron
Mar 23, 2004·Annual Review of Immunology·Meinrad Busslinger
Sep 1, 2005·Biochemical and Biophysical Research Communications·Robert Roskoski
Jun 9, 2007·British Journal of Haematology·Alberto OrfaoUNKNOWN REMA
Aug 8, 2008·Blood·Dean D Metcalfe

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Citations

Jun 8, 2013·Protein Engineering, Design & Selection : PEDS·F MimotoK Hattori

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