Human neutrophils express low levels of Fc?RIIIA, which plays a role in PMN activation.

ABSTRACT: We have identified a rare healthy Fc?RIIIB (CD16B)-null donor completely lacking FCGR3B RNA and protein expression and dissected the role of the different neutrophil Fc? receptors in the response to therapeutic anti-CD20 monoclonal antibodies. We observed that polymorphonuclear neutrophils (PMNs) from Fc?RIIIB 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 Fc?RIIIA (CD16A) on PMNs. Indeed, we demonstrated by reverse-transcription polymerase chain reaction, flow cytometry, and western blot analysis that PMNs from Fc?RIIIB WT donors and the null individual express low levels of Fc?RIIIA on their surfaces. Fc?RIIIA 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 Fc?RIIIB-null donor. Use of blocking anti-CD16 and anti-CD32 antibodies showed that Fc?RIIIA is also a major mediator of phagocytosis of CD20-opsonized beads by Fc?RIIIB WT and null PMNs. In contrast, trogocytosis of antibody-opsonized CLL B cells by PMNs was mediated primarily by Fc?RIIIB in WT PMNs and by Fc?RIIA in null PMNs. We conclude that Fc?RIIIA is an important player in PMN functions, whereas Fc?RIIIB is dispensable for activation and phagocytosis. We discuss the clinical implications of these findings.

SUBMITTER: Golay J 

PROVIDER: S-EPMC6484458 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature