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Ligand binding to FcγR induces c-myc-dependent apoptosis in IL-2-stimulated NK cells

Journal of Immunology, ISSN: 0022-1767, Vol: 154, Issue: 2, Page: 491-499
1995
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Article Description

The role of signals transduced via FcγRIIIA in the modulation of the proliferative potential of NK cells has been investigated. FcγR stimulation does not induce NK cell proliferation, and inhibits that induced by IL-2, but not by IL-12, as measured by [H]TdR incorporation, without affecting entrance or progression through cell cycle. The inhibitory effect depends, at least in part, on induced apoptosis of the cells, detected by both light and electron microscopy examination. FcγR stimulation induces apoptosis only in NK cells that have been previously activated by IL-2: this occurs within 3 h from receptor stimulation and is independent from de novo receptor-induced RNA or protein synthesis, but requires receptor-induced activation of protein tyrosine kinases and extracellular Ca influx. IL-2 induces accumulation of c-myc mRNA in NK cells, and treatment of the cells with c-myc antisense oligodeoxyribonucleotides during the IL-2 stimulation phase inhibits the susceptibility to FcγRIIIA-induced cell death, indicating that the induction of sustained levels of this proto-oncogene is necessary for the phenomenon. Thus, a two-step model is suggested for the FcyR-induced apoptosis in IL-2 activated NK cells: the first step involves induced expression of c-myc, and possibly other permissive factors, upon IL-2 prestimulation; the second depends directly on the stimulation of the receptor, independently of additional gene induction. The evidence presented here suggests a mechanism of control of NK cell expansion at the latest stages of Ab-dependent immune responses.

Bibliographic Details

Livio Azzoni; Bruno Calabretta; Bice Perussia; Ignacio Anegon

Medicine; Immunology and Microbiology

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