Evolution of immunoglobulin M (IgM) structure and function in vertebrates: A comprehensive review.

Immunoglobulin M (IgM), one of the most ancient and conserved antibody classes in vertebrates, plays a pivotal role in both innate and adaptive immunity. As the first antibody isotype to emerge in jawed vertebrates, IgM has undergone sophisticated structural and functional adaptations throughout its 500-million-year evolutionary history. This review systematically examines the evolutionary trajectory of IgM from cartilaginous fish to mammals through integrated structural and functional perspectives, elucidating the intrinsic relationship between its multimeric structural variations and functional specialization. Building upon comprehensive synthesis of existing knowledge, we propose a novel hypothesis explaining how IgM multimerization patterns co-evolved with functional specialization, and outline promising future research directions. Understanding IgM's evolution provides insights into the origins of adaptive immunity and the development of novel therapeutic strategies.