Fab-arm exchange is a misnomer.

There is increasing research activity aimed at understanding the molecular mechanisms underlying the phenomenon of so-called Fab-arm exchange, which has important implications for immunotherapies involving the anti-inflammatory IgG4 antibodies, and might also be relevant to our understanding of the etiology of the newly-described IgG4-related disease. I would like to point out that “Fab”-arm exchange is a misnomer and is misleading. It implies that only the Fab portion of the antibody is being exchanged; in fact, this dynamic process involves also the exchange of the Fc segment. The assumption underlying the coinage of Fab-arm exchange, I presume, was that the Fc portion of the IgG4 antibodies is identical and therefore, functionally, only the Fab is being exchanged. This assumption, however, ignores the presence of two isoallotypes on IgG4—valine309/leucine309 and arginine409/lysine409. Thus, IgG4 molecules in a person heterozygous at these loci would have Fc of distinct genotypes. Interestingly, one of these Fc genotypes has been shown to have a functional impact on “Fab”-arm exchange: the arginine409 allele enables the Fab-arm exchange, while the lysine409 allele abrogates it. Thus, in view of the fact that this phenomenon is restricted to the antibodies of IgG4 subclass and that genetically distinct Fab and Fc segments of the antibody are being exchanged, I suggest that Fab-arm exchange be changed to IgG4-arm exchange.