CoChat
Sign Up
PreprintCited by 47Monoclonal and Polyclonal Antibodies ResearchT-cell and B-cell ImmunologyBiomarkers in Disease Mechanisms

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

CD5L is a canonical component of circulatory IgM

Open access
Oskam, Nienke, den Boer, Maurits A., Lukassen, Marie V., Heer, Pleuni Ooijevaar-de, Veth, Tim S., Mierlo, Gerard van, Lai, Szu-Hsueh, Derksen, Ninotska I.L., Yin, Victor C., Streutker, Marij, Franc, Vojtech, Siborova, Marta, Damen, Mirjam, Kos, Dorien, Barendregt, Arjan, Bondt, Albert, Goudoever, Johannes B. van, 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
DOI 10.1101/2023.05.27.542462PMC PMC10723121

Preprint — published as 10.1073/pnas.2311265120

Open this paper in CoChat — free account

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 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 CD5 antigen-like (CD5L, 36 kDa) protein. 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 (pIgR). 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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2023.05.27.542462

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 57

  1. 10.1002/JLB.3RI0519-161R · DOI
  2. 10.1007/s10875-014-0025-4 · DOI
  3. 2014, The Long Elusive IgM Fc Receptor, FcμR, J. Clin. Immunol, 34, 35, 10.1007/s10875-014-0022-7 · DOI
  4. 10.1016/j.molimm.2011.05.011 · DOI
  5. 10.3390/v10040141 · DOI
  6. 2008, Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities. Clin. Exp. Immunol, 151, 42
  7. 2020, Changes in Human Milk Immunoglobulin Profile During Prolonged Lactation, Front. Pediatr, 8, 1
  8. 2020, Human Secretory IgM: An Elusive Player in Mucosal Immunity, Trends Immunol, 41, 141, 10.1016/j.it.2019.12.005 · DOI
  9. Keyt, B. A. , Baliga, R. , Sinclair, A. M. , Carroll, S. F. & Peterson, M. S. Structure, Function, and Therapeutic Use of IgM Antibodies. Antibodies 9, 53 (2020). · DOI
  10. 1998, Production of IgM hexamers by normal and autoimmune B cells: implications for the physiologic role of hexameric IgM, J. Immunol, 161, 4091, 10.4049/jimmunol.161.8.4091 · DOI
  11. 10.1111/j.1365-3083.1975.tb02620.x · DOI
  12. 1994, IgM hexamers? Immunol, Today, 15, 165
  13. 10.1002/1521-4141(200206)32:6<1802::AID-IMMU1802>3.0.CO;2-C · DOI
  14. 10.4049/jimmunol.2101196 · DOI
  15. 10.1073/pnas.1901841116 · DOI
  16. 2021, Structure of the human secretory immunoglobulin M core, Structure, 29, 564, 10.1016/j.str.2021.01.002 · DOI
  17. 2022, Cryomicroscopy reveals the structural basis for a flexible hinge motion in the immunoglobulin M pentamer, Nat. Commun, 13, 6314, 10.1038/s41467-022-34090-2 · DOI
  18. 10.1126/sciadv.aau1199 · DOI
  19. 10.1126/science.aaz5425 · DOI
  20. 10.1111/j.0001-2815.2004.00193.x · DOI
  21. 10.1074/jbc.272.10.6151 · DOI
  22. 10.1016/j.celrep.2013.03.006 · DOI
  23. 2019, Assessment of Apoptosis Inhibitor of Macrophage/CD5L as a Biomarker to Predict Mortality in the Critically Ill With Sepsis, Chest, 156, 696, 10.1016/j.chest.2019.04.134 · DOI
  24. 2018, Elevation of serum CD5L concentration is correlated with disease activity in patients with systemic lupus erythematosus, Int. Immunopharmacol, 63, 311, 10.1016/j.intimp.2018.07.022 · DOI
  25. 10.1189/jlb.3RU0215-074R · DOI
  26. 10.3390/ijms22031010 · DOI
  27. 10.1016/j.cell.2015.10.068 · DOI
  28. 2020, Resolving heterogeneous macromolecular assemblies by Orbitrap-based single-particle charge detection mass spectrometry, Nat. Methods, 17, 395, 10.1038/s41592-020-0770-7 · DOI · Paper page
  29. Young, G. et al. Quantitative mass imaging of single biological macromolecules. Science (80-.). 360, 423–427 (2018). · DOI
  30. 10.1084/jem.189.2.413 · DOI
  31. 2018, Structural investigation of human S. aureus-targeting antibodies that bind wall teichoic acid, MAbs, 10, 979
  32. 2021, A serum proteome signature to predict mortality in severe covid-19 patients, Life Sci. Alliance, 4, 1
  33. 10.1016/j.cels.2021.05.005 · DOI · Paper page
  34. 10.15252/emmm.202114123 · DOI
  35. 10.1038/s41598-018-23276-8 · DOI
  36. 10.1096/fj.201700941RR · DOI
  37. 10.1038/s41598-016-0001-8 · DOI · Paper page
  38. 2018, Activation of apoptosis inhibitor of macrophage is a sensitive diagnostic marker for NASH-associated hepatocellular carcinoma, J. Gastroenterol, 53, 770, 10.1007/s00535-017-1398-y · DOI
  39. 2021, CD5L deficiency attenuate acetaminophen-induced liver damage in mice via regulation of JNK and ERK signaling pathway, Cell Death Discov, 7, 1
  40. 10.1186/1559-0275-11-1 · DOI
  41. 2020, Plasma CD5L and non-invasive diagnosis of acute heart rejection, J. Hear. Lung Transplant, 39, 257, 10.1016/j.healun.2019.11.004 · DOI
  42. 10.1126/science.1144603 · DOI
  43. 2023, Identification of common and distinct origins of human serum and breastmilk IgA1 by mass spectrometry-based clonal profiling, Cell. Mol. Immunol, 20, 26
  44. 2020, DIA-NN: neural networks and interference correction enable deep proteome coverage in high throughput, Nat. Methods, 17, 41, 10.1038/s41592-019-0638-x · DOI
  45. 2008, MaxQuant enables high peptide identification rates, individualized p, p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol, 26, 1367
  46. 10.4049/jimmunol.2101196 · DOI
  47. 2023, Promoting Fc-Fc interactions between anti-capsular antibodies provides strong immune protection against Streptococcus pneumoniae, Elife, 12, 1
  48. 2015, Site-Specific Biotinylation of Purified Proteins Using BirA, in Site-Specific Protein Labeling: Methods and Protocols, 1266, 171, 10.1007/978-1-4939-2272-7_12 · DOI
  49. Großerichter-wagener, C. et al. Biased anti-idiotype response in rabbits leads to high-affinity monoclonal antibodies to biologics. MAbs 12, (2020). · DOI
  50. 2020, Resolving heterogeneous macromolecular assemblies by Orbitrap-based single-particle charge detection mass spectrometry, Nat. Methods, 17, 395, 10.1038/s41592-020-0770-7 · DOI · Paper page
  51. Koers, J. et al. CD45RB Glycosylation and Ig Isotype De fine Maturation of Functionally Distinct B Cell Subsets in Human Peripheral Blood. 13, 1–8 (2022). · DOI
  52. Unger, P. P. A. et al. Minimalistic in vitro culture to drive human naive b cell differentiation into antibody-secreting cells. Cells 10, (2021). · DOI
  53. 2021, Method for Depletion of IgG and IgM from Human Serum as Naive Complement Source, in Methods in Molecular Biology, 2227, 21, 10.1007/978-1-0716-1016-9_2 · DOI
  54. 10.15252/embj.201899894 · DOI
  55. 10.1038/S41586-021-03819-2 · DOI · Paper page
  56. 2022, Cryomicroscopy reveals the structural basis for a flexible hinge motion in the immunoglobulin M pentamer, Nat. Commun, 13, 6314, 10.1038/s41467-022-34090-2 · DOI
  57. 10.1002/jcc.20084 · DOI

Metadata

Authors
Oskam, N., den Boer, M. A., Lukassen, M. V., Heer, P. O.-D., Veth, T. S., Mierlo, G. V., Lai, S.-H., Derksen, N. I. L., Yin, V. C., Streutker, M., Franc, V., Siborova, M., Damen, M., Kos, D., Barendregt, A., Bondt, A., Goudoever, J. B. V., Haas, C. J. C., Aerts, P. C., Muts, R. M., Rooijakkers, S. H. M., Vidarsson, G., Rispens, T., & Heck, A. J. R.
Affiliations
  • Amsterdam UMC Location University of Amsterdam (NL)
  • Utrecht University (NL)
Corresponding author
  • Rispens, Theo
  • Heck, Albert J.R.
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
openRxiv
Published
2023-05-27
Volume
120
Issue
50
Pages
e2311265120-e2311265120
ISSN
0027-8424 (ISSN-L)
DOI
10.1101/2023.05.27.542462
PMC
PMC10723121
OpenAlex
W4389372115
Cited by
47
References
1
Citations by year
2026: 15 · 2025: 17 · 2024: 12 · 2023: 2
FWCI
7.62
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, other-oa)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
Funders
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (SPI.2017.028, 184.034.019)
  • Dutch Arthritis Association (17-2-404)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
Keywords
CD5L, apoptosis inhibitor of macrophage, immunoglobulin M, J chain, pentameric IgM, secretory IgM, FcμR, polymeric immunoglobulin receptor, humoral immunity
MeSH terms
Antigens, B-Lymphocytes, Immunoglobulin M, Immunoglobulin J-Chains, Macrophages

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review