CD5L associates with IgM via the J chain.

Area of Science:

• Immunology
• Structural Biology
• Molecular Mechanisms

Background:

• CD5 antigen-like (CD5L) is a known component of serum immunoglobulin M (IgM).
• The precise molecular interaction between CD5L and IgM has not been elucidated.
• Understanding this interaction is crucial for deciphering CD5L's role in immune function.

Purpose of the Study:

• To determine the structural basis of the CD5L-IgM complex.
• To investigate the functional consequences of CD5L binding to IgM.
• To clarify the role of the J chain in IgM-CD5L interactions.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was employed to visualize the human IgM pentamer core in complex with CD5L.
• Biochemical assays were used to assess binding affinities and functional impacts.
• Calcium ion (Ca2+) dependency was investigated.

Main Results:

• The cryo-EM structure revealed that CD5L binds to the J chain of IgM in a Ca2+-dependent manner.
• CD5L forms a disulfide bond with IgM, stabilizing the complex.
• CD5L reduces IgM binding to pIgR but does not affect binding to FcμR or IgM-mediated complement activation.

Conclusions:

• CD5L interacts with the IgM J chain through a Ca2+-dependent mechanism and a disulfide bond.
• CD5L modulates IgM's interaction with the mucosal transport receptor pIgR.
• These findings provide new insights into the function of CD5L and the IgM J chain in the immune system.