Sanquin and Utrecht University rewrite biology textbooks

Immunoglobulin M (IgM), a cornerstone of the immune system, has long been depicted in textbooks as a pentameric or hexameric protein complex. However, a recent discovery by researchers at Sanquin and Utrecht University has challenged this, revealing a surprising association with a small protein known as CD5L, thereby rewriting biology textbooks.

Principal investigator Theo Rispens and PhD student Nienke Oskam of Sanquin Research, together with the Heck Lab at Utrecht University, demonstrated that circulatory IgM exists exclusively as a complex of J-chain-containing pentamers covalently bound to CD5L. This molecule was overlooked for decades by many researchers worldwide.

Intriguingly, CD5L integration appears to have functional implications, diminishing IgM's binding to two of its receptors, FcαµR and the polymeric Immunoglobulin receptor. These receptors play crucial roles in IgM's effector functions, including neutralizing pathogens and activating complement cascades.

These findings redefine our understanding of IgM's composition and function, raising questions about the physiological significance of CD5L's association with IgM. Further research is warranted to elucidate the molecular mechanisms underlying its impact on immune responses. The research is published in PNAS.