The Functional Properties of IgG4 and the IgG4-Related Diseases The Immunologist's Point of View

The IgG4 subclass accounts only for a small amount of total IgG (3-5%) and exhibits poor effector properties with regard to complement and FcRgamma activation. Yet since 10 years an increasing number of reports has defined a new set of IgG4-related diseases (IgG4-RD) characterised by elevated serum IgG4 levels and diffuse or nodular lympho-plasmocytic infiltrates (>40% IgG4+ plasma cells) in various, mainly exocrine organs. The infiltrates are typically associated with a chronic-fibrosing inflammation. While the serum IgG4+ fraction is not always increased it contains an increased proportion of various autoantibodies. Here we review the structural properties of the IgG4 molecule and the factors regulating class-switch to IgG4 and we discuss how the unique property of IgG4 to undergo Fab-arm exchange may influence the peripheral B cell tolerance and impact on the immunopathology of IgG4-RD.