CD5L associates with IgM via the J chain

CD5 antigen-like (CD5L), also known as Spα or AIM (Apoptosis inhibitor of macrophage), emerges as an integral component of serum immunoglobulin M (IgM). However, the molecular mechanism underlying the interaction between IgM and CD5L has remained elusive. In this study, we present a cryo-electron microscopy structure of the IgM pentamer core in complex with CD5L. Our findings reveal that CD5L binds to the joining chain (J chain) in a Ca 2+ -dependent manner and further links to IgM via a disulfide bond. We further show that CD5L reduces IgM binding to the mucosal transport receptor pIgR, but does not impact the binding of the IgM-specific receptor FcμR. Additionally, CD5L does not affect IgM-mediated complement activation. These results offer new insights into our understanding of IgM and shed light on the functions of the IgM–CD5L complex in the immune system.