CD5L is a canonical component of circulatory IgM

Nienke Oskam, Maurits A. den Boer, Marie V. Lukassen, Pleuni Ooijevaar-De Heer, Tim S. Veth, Gerard van Mierlo, Szu Hsueh Lai, Ninotska I.L. Derksen, Victor Yin, Marij Streutker, Vojtech Franc, Marta Šiborová, Mirjam J.A. Damen, Dorien Kos, Arjan Barendregt, Albert Bondt, Johannes B. van Goudoever, Carla J.C. de Haas, Piet C. Aerts, Remy M. MutsSuzan H.M. Rooijakkers, Gestur Vidarsson, Theo Rispens, Albert J.R. Heck

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2 引文 斯高帕斯(Scopus)

摘要

Immunoglobulin M (IgM) is an evolutionary conserved key component of humoral immunity, and the first antibody isotype to emerge during an immune response. IgM is a large (1 MDa), multimeric protein, for which both hexameric and pentameric structures have been described, the latter additionally containing a joining (J) chain. Using a combination of single-particle mass spectrometry and mass photometry, proteomics, and immunochemical assays, we here demonstrate that circulatory (serum) IgM exclusively exists as a complex of J-chain-containing pentamers covalently bound to the small (36 kDa) protein CD5 antigen-like (CD5L, also called apoptosis inhibitor of macrophage). In sharp contrast, secretory IgM in saliva and milk is principally devoid of CD5L. Unlike IgM itself, CD5L is not produced by B cells, implying that it associates with IgM in the extracellular space. We demonstrate that CD5L integration has functional implications, i.e., it diminishes IgM binding to two of its receptors, the FcαµR and the polymeric Immunoglobulin receptor. On the other hand, binding to FcµR as well as complement activation via C1q seem unaffected by CD5L integration. Taken together, we redefine the composition of circulatory IgM as a J-chain containing pentamer, always in complex with CD5L.

原文English
文章編號e2311265120
期刊Proceedings of the National Academy of Sciences of the United States of America
120
發行號50
DOIs
出版狀態Published - 2023

All Science Journal Classification (ASJC) codes

  • 多學科

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