Production and characterization of mice transgenic for the A and B isoforms of human FcγRIII

Ar, Amoroso; Rk, Alpaugh; Mw, Barth; Am, McCall; Weiner, Louis M.

doi:10.1007/s002620050621

Cited by 8 publications

(1 citation statement)

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“…Similarly, the study of possible expression of low levels of FcgRIIIA in PMNs of transgenic mice or of cynomolgus monkeys, which lack CD16B, is warranted to generate tools to further dissect the role of this family of receptors in PMN functions. 53,54 Figure 7 summarizes the findings reported in this article: that PMNs express low levels of FcgRIIIA, which nonetheless may be a signaling molecule for neutrophil activation and phagocytosis of IgG-opsonized targets by these cells. In contrast, FcgRIIIB is very abundant on WT PMNs and mediates efficient binding to IgG-opsonized targets and subsequent trogocytosis.…”

Section: Discussionmentioning

confidence: 81%

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

Golay

Valgardsdóttir

Musaraj

et al. 2019

Blood

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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.

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Section: Discussionmentioning

confidence: 81%