IgG-effector functions: "the good, the bad and the ugly"

Area of Science:

• Immunology
• Molecular Biology

Background:

• Immunoglobulin G (IgG) antibodies are key mediators of host protection.
• IgG effector functions depend on interactions between the Fc-part and complement or cellular receptors, notably Fc gamma receptors (FcγRs).

Purpose of the Study:

• To review the critical factors influencing IgG-mediated immune responses.
• To focus on IgG3 variability and IgG-Fc glycosylation's impact on FcγR binding and effector functions.

Main Methods:

• Review of existing literature on IgG structure-function relationships.
• Analysis of factors affecting IgG effector functions, including FcγR interactions and IgG polymorphisms.

Main Results:

• Leukocyte FcγR expression, affinity, and genetic polymorphisms significantly influence IgG effector functions.
• Endogenous IgG polymorphisms (e.g., IgG3) and post-transcriptional modifications like Fc-glycosylation critically affect IgG-FcγR interactions and biological outcomes.

Conclusions:

• Variability in IgG3 half-life and placental transport, along with altered IgG-quality due to glycosylation, have significant clinical consequences.
• Understanding IgG quality is essential for predicting and potentially manipulating immune responses.