Immunoglobulin D and its encoding genes: An updated review.

Since the identification of a functional Cδ gene in ostriches, immunoglobulin (Ig) D has been considered to be an extremely evolutionarily conserved Ig isotype besides the IgM found in all classes of jawed vertebrates. However, in contrast to IgM (which remains stable over evolutionary time), IgD shows considerable structural plasticity among vertebrate species and, moreover, its functions are far from elucidated even in humans and mice. Recently, several studies have shown that high expression of the IgD-B-cell receptor (IgD-BCR) may help physiologically autoreactive B cells survive in peripheral lymphoid tissues thanks to unresponsiveness to self-antigens and help their entry into germinal centers to "redeem" autoreactivity via somatic hypermutation. Other studies have demonstrated that secreted IgD may enhance mucosal homeostasis and immunity by linking B cells with basophils to optimize T-helper-2 cell-mediated responses and to constrain IgE-mediated basophil degranulation. Herein, we review the new discoveries on IgD-encoding genes in jawed vertebrates in the past decade. We also highlight advances in the functions of the IgD-BCR and secreted IgD in humans and mice.
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