Human neutrophils express low levels of FcγRIIIA, which plays a role in PMN activation

We have identified a rare healthy FcγRIIIB (CD16B)-null donor completely lacking FCGR3B RNA and protein expression and dissected the role of the different neutrophil Fcγ receptors in the response to therapeutic anti-CD20 monoclonal antibodies. We observed that polymorphonuclear neutrophils (PMNs) fr...

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Bibliographic Details
Published in:Blood 2019-03, Vol.133 (13), p.1395-1405
Main Authors: Golay, Josée, Valgardsdottir, Rut, Musaraj, Gerta, Giupponi, Damiano, Spinelli, Orietta, Introna, Martino
Format: Article
Language:English
Subjects:
Cells, Cultured
Gene Deletion
Gene Expression
Humans
Immunoglobulin G - immunology
Leukemia, Lymphocytic, Chronic, B-Cell - genetics
Leukemia, Lymphocytic, Chronic, B-Cell - immunology
Neutrophils - immunology
Neutrophils - metabolism
Phagocytosis
Plenary Paper
Receptors, IgG - genetics
Receptors, IgG - immunology
RNA, Messenger - genetics
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Summary:We have identified a rare healthy FcγRIIIB (CD16B)-null donor completely lacking FCGR3B RNA and protein expression and dissected the role of the different neutrophil Fcγ receptors in the response to therapeutic anti-CD20 monoclonal antibodies. We observed that polymorphonuclear neutrophils (PMNs) from FcγRIIIB wild-type (WT) individuals or the null donor were more effectively activated by chronic lymphocytic leukemia (CLL) B-cell targets opsonized with glycoengineered anti-CD20 antibodies compared with fully core-fucosylated anti-CD20 antibodies, suggesting the presence and role of FcγRIIIA (CD16A) on PMNs. Indeed, we demonstrated by reverse-transcription polymerase chain reaction, flow cytometry, and western blot analysis that PMNs from FcγRIIIB WT donors and the null individual express low levels of FcγRIIIA on their surfaces. FcγRIIIA is a functional and activating molecule on these cells, because anti-CD16 F(ab′)2 antibodies alone were able to activate highly purified PMNs from the FcγRIIIB-null donor. Use of blocking anti-CD16 and anti-CD32 antibodies showed that FcγRIIIA is also a major mediator of phagocytosis of CD20-opsonized beads by FcγRIIIB WT and null PMNs. In contrast, trogocytosis of antibody-opsonized CLL B cells by PMNs was mediated primarily by FcγRIIIB in WT PMNs and by FcγRIIA in null PMNs. We conclude that FcγRIIIA is an important player in PMN functions, whereas FcγRIIIB is dispensable for activation and phagocytosis. We discuss the clinical implications of these findings. •Human neutrophils express low levels of FcγRIIIA, which are usually masked by the high levels of homologous FcγRIIIB.•FcγRIIIA, but not FcγRIIIB, appears to mediate neutrophil activation by IgG antibodies, as well as phagocytosis of antibody-opsonized beads. [Display omitted]
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2018-07-864538