Regulation of Human Natural Cytotoxicity by IgG

Sulica, Andrei; Galatiuc, Cecilia; Manciulea, Mioara; Bancu, Alexandru; DeLeo, Albert B.; Whiteside, Theresa L.; Herberman, Ronald B.

doi:10.1006/cimm.1993.1079

Cited by 10 publications

(4 citation statements)

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“…In addition, two-color flow cytometric studies indicate that virtually all CD16' peripheral blood mononuclear cells (PBMC) react with anti-human IgG, presumably due to the presence on their surface of cytophilic Ig acquired in vivo [13]. More recent findings emphasize the relatively high affinity constant of mIgG attachment to human NK cells [14] and the reciprocal inhibition of binding of mIgG and 3G8 mAb to FcyRIIIA on NK cells [15]. In addition, some cytophilic human IgG Ab have the ability to arm FcyR+ NK cells for subsequent attachment of soluble or cellular antigens and for reverse ADCC with antigenpositive target cells [ 161.…”

Section: Introductionmentioning

confidence: 99%

Divergent effects of FcγRIIIA ligands on the functional activities of human natural killer cells in vitro

Sulica¹,

Metes²,

Gherman³

et al. 1996

Eur J Immunol

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The Fc gamma receptor (R)IIIA (CD 16) plays an important role in regulating the cytotoxic and non-cytotoxic functions of human natural killer (NK) cells. Some anti-CD 16 monoclonal antibodies (mAb) have been shown to stimulate NK activity, while human monomeric (m) IgG induces dose-dependent inhibition of NK activity. To explore further these interactions mediated via Fc gamma RIIIA, purified NK cells were cultured for 2-3 days in the presence of mIgG, 3G8 mAb, interleukin-2 (IL-2) or a combination of mIgG or 3G8 with IL-2. Binding of mIgG or 3G8 to Fc gamma RIIIA induced divergent effects of functions of cultured NK cells: 3G8 mAb + IL-2 induced dose-dependent inhibition of proliferation attributable to apoptosis; in contrast, mIgG + IL-2 significantly increased NK cell proliferation. Incubation of NK cells in the presence of mIgG up-regulated expression of surface activation markers (CD69, IL-2R alpha, ICAM-1), cytotoxicity, cytokine production (IL-1 beta, IFN-gamma and TNF-alpha) and release of soluble IL-2R. Thus, mIgG binding to Fc gamma RIIIA induced stimulatory signals in human NK cells, leading to up-regulation of IL-2R alpha expression, cell proliferation and cytokine release.

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Section: Introductionmentioning

confidence: 99%

Divergent effects of FcγRIIIA ligands on the functional activities of human natural killer cells in vitro

Sulica¹,

Metes²,

Gherman³

et al. 1996

Eur J Immunol

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“…This is probably due to limitations of staining human NK cells by unlabeled human antibodies which requires anti-human secondary antibody staining. Since NK cells are coated with human immunoglobulins, 30 , 31 the non-specific background staining with secondary antihuman antibodies is high, seemingly masking any specific binding.…”

Section: Discussionmentioning

confidence: 99%

Anti-RhD antibody therapy modulates human natural killer cell function

Elias¹,

Kol²,

Kahlon³

et al. 2020

haematol

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Anti-RhD antibodies are widely used in clinical practice to prevent immunization against RhD, principally in hemolytic disease of the fetus and newborn. Intriguingly, this disease is induced by production of the very same antibodies when an RhD negative woman is pregnant with an RhD positive fetus. Despite over five decades of use, the mechanism of this treatment is, surprisingly, still unclear. Here we show that anti-RhD antibodies induce human natural killer (NK) cell degranulation. Mechanistically, we demonstrate that NK cell degranulation is mediated by binding of the Fc segment of anti-RhD antibodies to CD16, the main Fcγ receptor expressed on NK cells. We found that this CD16 activation is dependent upon glycosylation of the anti-RhD antibodies. Furthermore, we show that anti-RhD antibodies induce NK cell degranulation in vivo in patients who receive this treatment prophylactically. Finally, we demonstrate that the anti-RhD drug KamRho enhances the killing of dendritic cells. We suggest that this killing leads to reduced activation of adaptive immunity and may therefore affect the production of anti-RhD antibodies.

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“…Although Fc receptor competition offers a compelling model for the mechanism of action of IVIg, several alternative models have also been postulated. There are reports that increased serum levels of IgG associated with IVIg infusion increases inhibitory ITAM signalling via FcγRIIIA which in turn reduces NK-mediated ADCC activity [ 157 , 214 ] and inflammatory responses [ 158 , 215 ]. Further supporting the notion of FcγRIIIA mediated effects are studies by Mimura et al, who found that afucosylated and galactosylated glycoforms of IVIg impeded ADCC activity with 20 times higher potency than native IgG [ 216 ].…”

Section: The Signal-to-noise Problem In Igg Signallingmentioning

confidence: 99%

Serum immunoglobulin and the threshold of Fc receptor-mediated immune activation

Bauer-Smith,

Sudol,

Beers

et al. 2023

Biochimica et Biophysica Acta (BBA) - General Subjects

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Regulation of Human Natural Cytotoxicity by IgG

Cited by 10 publications

References 0 publications

Divergent effects of FcγRIIIA ligands on the functional activities of human natural killer cells in vitro

Divergent effects of FcγRIIIA ligands on the functional activities of human natural killer cells in vitro

Anti-RhD antibody therapy modulates human natural killer cell function

Serum immunoglobulin and the threshold of Fc receptor-mediated immune activation

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