Four keys to unlock IgG

Abstract

The identification of discrete subclasses within the immunoglobulin G (IgG) isotype by Grey and Kunkel (1964. J. Exp. Med.https://doi.org/10.1084/jem.120.2.253) provided the framework for our current understanding of differential IgG subclass activity in protective and self-reactive immune responses.

Insights from Falk Nimmerjahn and Jeffrey V. Ravetch.

The complexity of IgG subclass activity. (A) Shown is an in-gel antibody precipitation assay (ouchterlony assay) from Grey and Kunkel (1964), demonstrating that a rabbit antiserum generated against one myeloma IgG molecule precipitates some but not all IgG antibodies derived from other multiple myeloma patients (IgG from patient We is not precipitated, whereas IgG from patients Ap, Fe, Hu, and FrII is precipitated). The antiserum also reacted against normal human serum demonstrating the presence of IgG subclasses in healthy individuals. (B) Depicted are lung melanoma metastases in C57BL/6- and FcγRIIb-deficient mice left untreated or treated with IgG subclass switch variants (IgG1 and IgG2a) of the melanoma-specific antibody TA99. (C) Shown are lung melanoma metastases in C57L/6 mice left untreated or treated with a TA99-IgG2b subclass variant carrying a sugar moiety with or without fucose in its Fc domain. (D) Schematic representation of factors influencing IgG activity. Apart from individual IgG subclasses, IgG glycosylation plays a major role in balancing the pro- and anti-inflammatory activities of IgG via modulating the interaction with type I and type II Fc-receptors (FcR). See text for further details.