IgM is an isotype of firsts.
On the cell surface, IgM consists of two identical μ heavy chains and two identical light chains
(μ2L2)
μ H chains are initially expressed on developing pre–B cells bound to surrogate light chain to form pre–B cell receptors. Pre–B cells that undergo successful light chain gene rearrangement replace surrogate light chain with either a κ or λ light chain to form an immature B cell.
在这一阶段,B 细胞尚未开始轻链基因(L chain)的重排,因此也就没有真实的轻链参与抗体的形成。为了测试 μ 链是否能够正确地发挥功能,前 B 细胞使用一种替代轻链(surrogate light chain),这是一种特殊的蛋白质,它结构上类似于真正的轻链。
On the B cell surface, IgM is noncovalently associated with two other polypeptide chains, Ig-α (CD79a) and Ig-β (CD79b). 158 - 160 These integral membrane proteins serve to transduce signals when surface IgM binds to and is cross-linked by cognate antigen
In the secreted form, IgM can consist of either pentamers (μ2L2)5 or, less often, hexamers (μ2L2)6.
The μ2L2 monomers of the pentameric form are linked one to another by disulfide bonds in the CH4 domains. Two of these monomers are, on one side, disulfide bonded not to another μ chain but to a 15,000-Da polypeptide, called J chain. The J chain is also found in dimeric IgA. There may be multiple patterns of such disulfide bonding, such that different cysteines participate in different monomeric units.
五聚体形式的μ2L2单体通过CH4结构域中的二硫键相互连接。其中两个单体的一侧不是与另一个μ链二硫键合,而是与一个15000 Da的多肽(称为J链)二硫键结合。J链也存在于二聚体IgA中。这种二硫键可能有多种模式,因此不同的半胱氨酸参与不同的单体单元。
The J chain caps the tailpiece assembly and bridges the interaction between IgM-Fc and the polymeric immunoglobulin receptor (pIgR), which undergoes a large conformational change to engage the IgM-J complex. pIgR is a type I transmembrane protein that contains five extracellular immunoglobulin-like domains (D1-D5). It binds to J chain–containing secretory IgM and IgA at the basolateral surface of epithelial cells and escorts them to the apical side. There, the ectodomain, termed the secretory component (SC), is released by proteolysis and secreted together with IgM and IgA.
J链覆盖尾片组件,并桥接IgM-Fc和聚合物免疫球蛋白受体(pIgR)之间的相互作用,pIgR经历了较大的构象变化以与IgM-J复合物结合。pIgR是一种I型跨膜蛋白,含有五个细胞外免疫球蛋白样结构域(D1-D5)。它与上皮细胞基底外侧表面的含J链的分泌型IgM和IgA结合,并将它们护送到顶端。在那里,外结构域被称为分泌成分(SC),通过蛋白水解释放,并与IgM和IgA一起分泌。