CD5L is a canonical component of circulatory IgM
Oskam, Nienke; den Boer, Maurits A.; Lukassen, Marie V.; Ooijevaar-De Heer, Pleuni; Veth, Tim S.; van Mierlo, Gerard; Lai, Szu Hsueh; Derksen, Ninotska I.L.; Yin, Victor; Streutker, Marij; Franc, Vojtech; Šiborová, Marta; Damen, Mirjam J.A.; Kos, Dorien; Barendregt, Arjan; Bondt, Albert; van Goudoever, Johannes B.; de Haas, Carla J.C.; Aerts, Piet C.; Muts, Remy M.; Rooijakkers, Suzan H.M.; Vidarsson, Gestur; Rispens, Theo; Heck, Albert J.R.
(2023) Proceedings of the National Academy of Sciences of the United States of America, volume 120, issue 50, pp. 1 - 7
(Article)
Abstract
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
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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.
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Keywords: IgM, CD5L, mass spectrometry, immunoglobulin, structure, General
ISSN: 0027-8424
Publisher: National Academy of Sciences
Note: Publisher Copyright: © 2023 National Academy of Sciences. All rights reserved.
(Peer reviewed)
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