Phospholipase Cγ2 Is Essential for Specific Functions of FcεR and FcγR

PLCγ2 is similarly required in other peripheral immune cells to enable calcium mobilization upon B cell receptor activation using anti-IgM, FcεR ligation by IgE in mast cells, and FcγR activation in macrophages.

“This observation adds to previous reports showing that PLCγ2 is similarly required in other peripheral immune cells to enable calcium mobilization upon B cell receptor activation using anti-IgM38, as well as FcεR ligation by IgE in mast cells and FcγR activation in macrophages10.”

PLCγ2-deficient mice are resistant to IgE-mediated cutaneous inflammatory skin reactions.

“The PLCγ2-deficient mice were also resistant to IgE-mediated cutaneous inflammatory skin reactions (71).”

PLCγ2 KO mice have normal numbers of myeloid cells, and mast cells exhibit normal MAPK activation and cytokine mRNA levels, but show impaired FcεR-stimulated calcium flux, IP3 production, degranulation, and inflammatory cytokine release.

“While PLCγ2 KO mice have normal numbers of myeloid cells, and mast cells exhibit normal MAPK activation and cytokine mRNA levels, they show impaired FcεR-stimulated calcium flux, IP3 production, degranulation, and inflammatory cytokine release (71).”

In monocytes, macrophages, and mast cells, PLCγ2 is activated through crosslinking of FcεR and FcγR.

“In monocytes, macrophages, and mast cells, PLCγ2 is activated through crosslinking of the FcεR and FcγR (71).”

PLCγ2 is implicated in allergic responses, specifically with regard to mast cell function and crosslinking of FcεRI and FcγR and subsequent degranulation.

“PLCγ2 is implicated in allergic responses, specifically with regard to the function of mast cells and their crosslinking of FcεRI (IgE-binding receptor) and FcγR and subsequent degranulation (71).”

PLCγ2 is more broadly present in myeloid cells, neutrophils, mast cells, NK cells, B-cells and platelets.

“On the other hand, PLCγ2 is more broadly present in myeloid cells [5, 25, 26], neutrophils [25, 27], mast cells [25], NK cells [5, 25], B-cells and platelets [5, 28, 29]”

In both humans and mice, PLCγ2 loss, as well as strong GOF, mostly results in detrimental and sometimes overlapping phenotypes, as largely described for the peripheral immune system.

“In both humans and mice, PLCγ2 loss, as well as strong GOF, mostly results in detrimental and sometimes overlapping phenotypes, as largely described for the peripheral immune system [5, 25]”

PLCγ2 LOF causes impaired Fc-receptor-mediated responses in mast cells, platelets and macrophages.

“PLCγ2 LOF causes impaired Fc-receptor-mediated responses in mast cells, platelets and macrophages [25]”