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.

自从在鸵鸟中鉴定出功能性 Cδ 基因以来，除了在所有种类的有颌脊椎动物中发现的 IgM 之外，免疫球蛋白 (Ig) D 已被认为是一种在进化上极为保守的 Ig 同种型。然而，与 IgM（在进化过程中保持稳定）相比，IgD 在脊椎动物物种中显示出相当大的结构可塑性，此外，即使在人类和小鼠中，其功能也远未阐明。最近，一些研究表明，由于对自身抗原无反应，IgD-B 细胞受体 (IgD-BCR) 的高表达可能有助于生理性自身反应性 B 细胞在外周淋巴组织中存活，并有助于它们进入生发中心“赎回”。 ” 自反应通过体细胞超突变。其他研究表明，分泌的 IgD 可通过将 B 细胞与嗜碱性粒细胞连接以优化 T-helper-2 细胞介导的反应并限制 IgE 介导的嗜碱性粒细胞脱粒，从而增强粘膜稳态和免疫。在此，我们回顾了过去十年在有颌脊椎动物中 IgD 编码基因的新发现。我们还强调了 IgD-BCR 功能的进展以及人类和小鼠中分泌的 IgD。