B-cell superantigens: implications for selection of the human antibody repertoire

For several decades, B-cell interactions with antigens were thought to occur only through a clonal activation mechanism, in which the hypervariable regions of the immunoglobulin receptor are exclusively involved in ligand binding. However, an additional mode of interaction can occur, whereby molecules, termed B-cell superantigens, can bind human B cells bearing immunoglobulin receptors of a given variable (V)-gene family. This mechanism requires contributions from regions outside the conventional hypervariable loops and results in a B-cell response of increased magnitude. Here, Moncef Zouali reviews recent in vitro and in vivo observations on human B-cell superantigens in the context of the current consensus of B-cell development, and discusses the implications of these novel concepts with respect to pathogenesis.