Blood. 2019 Jan 17. pii: blood-2018-07-864538. doi: 10.1182/blood-2018-07-864538. [Epub ahead of print]
Human neutrophils express low levels of Fc?RIIIA, which plays a role in PMN activation.
Golay J1, Valgardsdottir R2, Musaraj G2, Giupponi D3, Spinelli O3, Introna M2.
1
Center of Cellular Therapy 'G. Lanzani', Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy; jgolay@asst-pg23.it.
2
Center of Cellular Therapy 'G. Lanzani', Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy.
3
Division of Hematology, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy.
We have identified a rare healthy Fc?RIIIB (CD16B) Null donor completely lacking FCGR3B RNA and protein expression and have dissected the role of the different neutrophil Fc gamma receptors in the response to therapeutic anti-CD20 monoclonal antibodies. We observed that PMN from either Fc?RIIIB wild type (WT) individuals or the Null donor were more effectively activated by CLL B-cell targets opsonized with glycoengineered compared to fully core-fucosylated anti-CD20 antibodies, suggesting the presence and role of Fc?RIIIA (CD16A) on PMN. Indeed we demonstrated by RT-PCR, flow cytometry and Western blot analysis that PMN from both Fc?RIIIB WT donors and the Null individual express low levels of Fc?RIIIA on their surface. Fc?RIIIA is a functional and activating molecule on these cells, since anti-CD16 F(ab')2 antibodies alone were able to activate highly purified PMN from the Fc?RIIIB Null donor. Use of blocking anti-CD16 and -CD32 antibodies showed that Fc?RIIIA is also a major mediator of phagocytosis of CD20 opsonized beads by both Fc?RIIIB WT and Null PMN. In contrast, trogocytosis of antibody opsonized CLL B-cells by PMN was mediated mostly by Fc?RIIIB in WT donors and Fc?RIIA in Null PMN, respectively. We conclude that Fc?RIIIA is an important player for PMN functions, whereas Fc?RIIIB is dispensable for activation and phagocytosis. We discuss the clinical implications of these findings. |
