Allelic polymorphisms in the FcγRIIC gene can influence its function on normal human natural killer cells

LK Ernst, D Metes, RB Herberman, PA Morel - Journal of molecular …, 2002 - Springer
LK Ernst, D Metes, RB Herberman, PA Morel
Journal of molecular medicine, 2002Springer
Natural killer (NK) cells are important in host defense against viruses and tumors and can
induce death of virally infected cells following engagement of cell surface receptors. Human
NK cells express receptors for the Fc portion of IgG which stimulate antibody-dependent cell-
mediated cytotoxicity and induce cytokine production. We have shown that NK cells from
certain individuals can express, in addition to CD16 (FcγRIIIa), isoforms of CD32 (FcγRIIc1-
4). Expression of CD32 on NK cells is dependent on an allelic polymorphism of the FcγRIIC …
Abstract
Natural killer (NK) cells are important in host defense against viruses and tumors and can induce death of virally infected cells following engagement of cell surface receptors. Human NK cells express receptors for the Fc portion of IgG which stimulate antibody-dependent cell-mediated cytotoxicity and induce cytokine production. We have shown that NK cells from certain individuals can express, in addition to CD16 (FcγRIIIa), isoforms of CD32 (FcγRIIc1-4). Expression of CD32 on NK cells is dependent on an allelic polymorphism of the FcγRIIC gene. We analyzed the expression and function of CD32 on NK cells from 31 normal donors. Fourteen of the 31 (45%) donors expressed CD32 on their NK cells. Molecular characterization of FcγRIIc isoforms expressed by the CD32+ donors revealed that the majority of donors expressed the FcγRIIc1 isoform. Interestingly, 3 of the 14 positive donors did not express FcγRIIc1, and we identified a novel isoform, FcγRIIc5, expressed by these individuals. The expression of this isoform was correlated to a second allelic polymorphism that controls exon splicing. One of the three was found to express FcγRIIb on the NK cells. Biochemical analysis revealed that CD32+ donors of both types expressed a 40-kDa protein, specifically immunoprecipitated by anti-CD32 monoclonal antibodies. Functionally, only individuals expressing the FcγRIIc1 isoform were able to trigger reverse antibody-dependent cell-mediated cytotoxicity via CD32 whereas a CD32+ individual expressing the FcγRIIb isoform was unable to trigger this function. These results demonstrate that the presence of multiple allelic polymorphisms in the FcγRIIC gene determine the expression and function of CD32 on NK cells.
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