Immunoglobulin isotypes: structure, function, and genetics.

Abstract

Immunoglobulin (Ig) classes (in mammals, IgM, IgA, IgD, IgG, IgE) are defined by the isotypes of heavy (H) chains (µ, α, δ, γ, and e). Each isotype is in turn distinguished by unique structures in its constant region domains. These different structures confer distinctive functions on the Ig classes. When two or more Ig classes are very similar, as occurs with the four different types of IgG found in man and mouse, they are usually termed subclasses. Each isotype is encoded by a distinct gene and multiple heavy chain isoforms can be produced by alternative pathways of RNA processing, such as the secreted (slg) and membrane (mlg) forms of all H chains, or the full-length and truncated H chain isoforms of certain avian antibodies. Allelic variation in the constant (C) regions gives rise to allotypes. The different types of light (L) chains (in mammals, к and λ) are also typically referred to as isotypes. This system of classification of Igs was developed from studies of man and his immunological understudy, the mouse, and has proven useful not only in these two species, but also in other mammalian species. Although the classification of mammalian Ig classes and isotypes is quite clear, the situation with Igs from nonmammalian vertebrates is not. For example, is the shark molecule referred to as IgM really IgM? Should we call the predominant low molecular weight Ig in chickens IgG or IgY? This chapter discusses the ways in which these and similar questions have been approached.