Control of B Cell Responsiveness by Isotype and Structural Elements of the Antigen Receptor

Expression of a functional B cell antigen receptor (BCR) plays a central role in regulating B cell development, maturation, and effector functions. Although IgM is solely expressed in immature B cell stages, the presence of both IgM- and IgD-BCR isotypes on mature naïve B cells raises the question of whether IgD has a unique role in B cell activation and function. While earlier studies suggested a broad functional redundancy between IgM and IgD, recent data point to an important immune regulatory role of IgD. Herein, we review these findings and discuss how the structural flexibility, mode of antigen binding, and co-receptor interactions, enable the IgD-BCR to act as a 'rheostat', regulating the activation and function of mature naïve B cells.