---
_id: '18109'
abstract:
- lang: eng
  text: Venous thromboembolism (VTE) is a common, deadly disease with an increasing
    incidence despite preventive efforts. Clinical observations have associated elevated
    antibody concentrations or antibody-based therapies with thrombotic events. However,
    how antibodies contribute to thrombosis is unknown. Here, we show that reduced
    blood flow enabled immunoglobulin M (IgM) to bind to FcμR and the polymeric immunoglobulin
    receptor (pIgR), initiating endothelial activation and platelet recruitment. Subsequently,
    the procoagulant surface of activated platelets accommodated antigen- and FcγR-independent
    IgG deposition. This leads to classical complement activation, setting in motion
    a prothrombotic vicious circle. Key elements of this mechanism were present in
    humans in the setting of venous stasis as well as in the dysregulated immunothrombosis
    of COVID-19. This antibody-driven thrombosis can be prevented by pharmacologically
    targeting complement. Hence, our results uncover antibodies as previously unrecognized
    central regulators of thrombosis. These findings carry relevance for therapeutic
    application of antibodies and open innovative avenues to target thrombosis without
    compromising hemostasis.
acknowledgement: "We thank Michael Carroll (Harvard Medical School, Boston) for providing
  Ighmtm1Che, C4−/−, and C3−/− mice; Mark Suter (University of Zurich, Zurich) for
  providing Aicda−/− mice; Marina Botto (Imperial College London, London) for providing
  C1q−/− and fB−/− mice; Craig Gerard (Harvard Medical School, Boston) for providing
  C3aR−/− mice; Falk Nimmerjahn (University Erlangen-Nuernberg, Erlangen) for providing
  Fcgr−/−Fcgr2b−/− mice; Karl Lang (University of Duisburg-Essen, Essen) for providing
  Fcmr−/− mice; Hans Hengartner and Rolf Zinkernagel (ETH Zurich, Zurich) for providing
  KL25 mice; Mark Zabel (University Hospital of Zurich, Zurich) for providing CR2−/−
  mice; Christie Ballantyne (Baylor College of Medicine, Houston) for providing CD11c−/−
  mice; and Siamon Gordon (University of Oxford, Oxford) for providing CD11b−/− mice.
  A.V. wishes to thank Michael Grünaug and dedicates this work to Annette, Rita, and
  Hans.\r\nThis project has received funding from the European Research Council (ERC)
  under the European Union’s Horizon 2020 research and innovation programme (grant
  agreement no. \r\n947611) (K.S.). This study was supported by the Deutsche Forschungsgemeinschaft
  through the collaborative research center 914 project B02 (K.S. and S.M.), project
  B04 (A.V.), project A01 (M.M.), project B01 (M.S.), the collaborative research center
  1123 project B07 (K.S. and S.M.), the collaborative research center 359 (project
  A03 [K.S.] and B02 [M.S.]), the international research training group 1911 project
  B09 (A.V.), the clinical research unit 303 project 7 (A.V.), cluster of excellence
  2167 (A.V.), collaborative research center 1526 project 05 (A.V.), the ANR-DFG project
  JAKPOT (K.S.), LMUexcellent (K.S.), and the Deutsche Zentrum für Herz-Kreislauf-Forschung
  (PostDoc Grant and partner site project [K.S. and S.M.]). M.I. is supported by the
  European Research Council (ERC) Advanced Grant 101141363, ERC Proof of Concept Grant
  101138728, Italian Association for Cancer Research (AIRC) Grants 19891 and \r\n22737,
  Italian Ministry for University and Research Grants PE00000007 (INF-ACT) and PRIN
  \r\n2022FMESXL, Funded Research Agreement from Asher Biotherapeutics, VIR Biotechnology,
  and BlueJay Therapeutics. V.F. is supported by the Italian Ministry for University
  and Research Grants PE00000007 (INF-ACT) and Fondazione Prossimo Mio."
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Konstantin
  full_name: Stark, Konstantin
  last_name: Stark
- first_name: Badr
  full_name: Kilani, Badr
  last_name: Kilani
- first_name: Sven
  full_name: Stockhausen, Sven
  last_name: Stockhausen
- first_name: Johanna
  full_name: Busse, Johanna
  last_name: Busse
- first_name: Irene
  full_name: Schubert, Irene
  last_name: Schubert
- first_name: Thuy Duong
  full_name: Tran, Thuy Duong
  last_name: Tran
- first_name: Florian R
  full_name: Gärtner, Florian R
  id: 397A88EE-F248-11E8-B48F-1D18A9856A87
  last_name: Gärtner
  orcid: 0000-0001-6120-3723
- first_name: Alexander
  full_name: Leunig, Alexander
  last_name: Leunig
- first_name: Kami
  full_name: Pekayvaz, Kami
  last_name: Pekayvaz
- first_name: Leo
  full_name: Nicolai, Leo
  last_name: Nicolai
- first_name: Valeria
  full_name: Fumagalli, Valeria
  last_name: Fumagalli
- first_name: Julia
  full_name: Stermann, Julia
  last_name: Stermann
- first_name: Felix
  full_name: Stephan, Felix
  last_name: Stephan
- first_name: Christian
  full_name: David, Christian
  last_name: David
- first_name: Martin B.
  full_name: Müller, Martin B.
  last_name: Müller
- first_name: Birgitta
  full_name: Heyman, Birgitta
  last_name: Heyman
- first_name: Anja
  full_name: Lux, Anja
  last_name: Lux
- first_name: Alexandra
  full_name: Da Palma Guerreiro, Alexandra
  last_name: Da Palma Guerreiro
- first_name: Lukas P.
  full_name: Frenzel, Lukas P.
  last_name: Frenzel
- first_name: Christoph Q.
  full_name: Schmidt, Christoph Q.
  last_name: Schmidt
- first_name: Arthur
  full_name: Dopler, Arthur
  last_name: Dopler
- first_name: Markus
  full_name: Moser, Markus
  last_name: Moser
- first_name: Sue
  full_name: Chandraratne, Sue
  last_name: Chandraratne
- first_name: Marie Luise
  full_name: Von Brühl, Marie Luise
  last_name: Von Brühl
- first_name: Michael
  full_name: Lorenz, Michael
  last_name: Lorenz
- first_name: Thomas
  full_name: Korff, Thomas
  last_name: Korff
- first_name: Martina
  full_name: Rudelius, Martina
  last_name: Rudelius
- first_name: Oliver
  full_name: Popp, Oliver
  last_name: Popp
- first_name: Marieluise
  full_name: Kirchner, Marieluise
  last_name: Kirchner
- first_name: Philipp
  full_name: Mertins, Philipp
  last_name: Mertins
- first_name: Falk
  full_name: Nimmerjahn, Falk
  last_name: Nimmerjahn
- first_name: Matteo
  full_name: Iannacone, Matteo
  last_name: Iannacone
- first_name: Markus
  full_name: Sperandio, Markus
  last_name: Sperandio
- first_name: Bernd
  full_name: Engelmann, Bernd
  last_name: Engelmann
- first_name: Admar
  full_name: Verschoor, Admar
  last_name: Verschoor
- first_name: Steffen
  full_name: Massberg, Steffen
  last_name: Massberg
citation:
  ama: Stark K, Kilani B, Stockhausen S, et al. Antibodies and complement are key
    drivers of thrombosis. <i>Immunity</i>. 2024;57(9):2140-2156. doi:<a href="https://doi.org/10.1016/j.immuni.2024.08.007">10.1016/j.immuni.2024.08.007</a>
  apa: Stark, K., Kilani, B., Stockhausen, S., Busse, J., Schubert, I., Tran, T. D.,
    … Massberg, S. (2024). Antibodies and complement are key drivers of thrombosis.
    <i>Immunity</i>. Elsevier. <a href="https://doi.org/10.1016/j.immuni.2024.08.007">https://doi.org/10.1016/j.immuni.2024.08.007</a>
  chicago: Stark, Konstantin, Badr Kilani, Sven Stockhausen, Johanna Busse, Irene
    Schubert, Thuy Duong Tran, Florian R Gärtner, et al. “Antibodies and Complement
    Are Key Drivers of Thrombosis.” <i>Immunity</i>. Elsevier, 2024. <a href="https://doi.org/10.1016/j.immuni.2024.08.007">https://doi.org/10.1016/j.immuni.2024.08.007</a>.
  ieee: K. Stark <i>et al.</i>, “Antibodies and complement are key drivers of thrombosis,”
    <i>Immunity</i>, vol. 57, no. 9. Elsevier, pp. 2140–2156, 2024.
  ista: Stark K, Kilani B, Stockhausen S, Busse J, Schubert I, Tran TD, Gärtner FR,
    Leunig A, Pekayvaz K, Nicolai L, Fumagalli V, Stermann J, Stephan F, David C,
    Müller MB, Heyman B, Lux A, Da Palma Guerreiro A, Frenzel LP, Schmidt CQ, Dopler
    A, Moser M, Chandraratne S, Von Brühl ML, Lorenz M, Korff T, Rudelius M, Popp
    O, Kirchner M, Mertins P, Nimmerjahn F, Iannacone M, Sperandio M, Engelmann B,
    Verschoor A, Massberg S. 2024. Antibodies and complement are key drivers of thrombosis.
    Immunity. 57(9), 2140–2156.
  mla: Stark, Konstantin, et al. “Antibodies and Complement Are Key Drivers of Thrombosis.”
    <i>Immunity</i>, vol. 57, no. 9, Elsevier, 2024, pp. 2140–56, doi:<a href="https://doi.org/10.1016/j.immuni.2024.08.007">10.1016/j.immuni.2024.08.007</a>.
  short: K. Stark, B. Kilani, S. Stockhausen, J. Busse, I. Schubert, T.D. Tran, F.R.
    Gärtner, A. Leunig, K. Pekayvaz, L. Nicolai, V. Fumagalli, J. Stermann, F. Stephan,
    C. David, M.B. Müller, B. Heyman, A. Lux, A. Da Palma Guerreiro, L.P. Frenzel,
    C.Q. Schmidt, A. Dopler, M. Moser, S. Chandraratne, M.L. Von Brühl, M. Lorenz,
    T. Korff, M. Rudelius, O. Popp, M. Kirchner, P. Mertins, F. Nimmerjahn, M. Iannacone,
    M. Sperandio, B. Engelmann, A. Verschoor, S. Massberg, Immunity 57 (2024) 2140–2156.
date_created: 2024-09-22T22:01:42Z
date_published: 2024-09-10T00:00:00Z
date_updated: 2025-09-08T09:50:13Z
day: '10'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1016/j.immuni.2024.08.007
external_id:
  isi:
  - '001317438500001'
  pmid:
  - '39226900'
file:
- access_level: open_access
  checksum: 4683de43d06a8fd8e3fc91af4ddc1ba2
  content_type: application/pdf
  creator: dernst
  date_created: 2024-09-30T09:16:03Z
  date_updated: 2024-09-30T09:16:03Z
  file_id: '18162'
  file_name: 2024_Immunity_Stark.pdf
  file_size: 6892750
  relation: main_file
  success: 1
file_date_updated: 2024-09-30T09:16:03Z
has_accepted_license: '1'
intvolume: '        57'
isi: 1
issue: '9'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '09'
oa: 1
oa_version: Published Version
page: 2140-2156
pmid: 1
publication: Immunity
publication_identifier:
  eissn:
  - 1097-4180
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Antibodies and complement are key drivers of thrombosis
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 57
year: '2024'
...
---
OA_place: publisher
OA_type: free access
_id: '7876'
abstract:
- lang: eng
  text: 'In contrast to lymph nodes, the lymphoid regions of the spleen—the white
    pulp—are located deep within the organ, yielding the trafficking paths of T cells
    in the white pulp largely invisible. In an intravital microscopy tour de force
    reported in this issue of Immunity, Chauveau et al. show that T cells perform
    unidirectional, perivascular migration through the enigmatic marginal zone bridging
    channels. '
article_processing_charge: No
article_type: original
author:
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
- first_name: Tim
  full_name: Lämmermann, Tim
  last_name: Lämmermann
citation:
  ama: 'Sixt MK, Lämmermann T. T cells: Bridge-and-channel commute to the white pulp.
    <i>Immunity</i>. 2020;52(5):721-723. doi:<a href="https://doi.org/10.1016/j.immuni.2020.04.020">10.1016/j.immuni.2020.04.020</a>'
  apa: 'Sixt, M. K., &#38; Lämmermann, T. (2020). T cells: Bridge-and-channel commute
    to the white pulp. <i>Immunity</i>. Elsevier. <a href="https://doi.org/10.1016/j.immuni.2020.04.020">https://doi.org/10.1016/j.immuni.2020.04.020</a>'
  chicago: 'Sixt, Michael K, and Tim Lämmermann. “T Cells: Bridge-and-Channel Commute
    to the White Pulp.” <i>Immunity</i>. Elsevier, 2020. <a href="https://doi.org/10.1016/j.immuni.2020.04.020">https://doi.org/10.1016/j.immuni.2020.04.020</a>.'
  ieee: 'M. K. Sixt and T. Lämmermann, “T cells: Bridge-and-channel commute to the
    white pulp,” <i>Immunity</i>, vol. 52, no. 5. Elsevier, pp. 721–723, 2020.'
  ista: 'Sixt MK, Lämmermann T. 2020. T cells: Bridge-and-channel commute to the white
    pulp. Immunity. 52(5), 721–723.'
  mla: 'Sixt, Michael K., and Tim Lämmermann. “T Cells: Bridge-and-Channel Commute
    to the White Pulp.” <i>Immunity</i>, vol. 52, no. 5, Elsevier, 2020, pp. 721–23,
    doi:<a href="https://doi.org/10.1016/j.immuni.2020.04.020">10.1016/j.immuni.2020.04.020</a>.'
  short: M.K. Sixt, T. Lämmermann, Immunity 52 (2020) 721–723.
date_created: 2020-05-24T22:00:57Z
date_published: 2020-05-19T00:00:00Z
date_updated: 2026-06-18T19:27:52Z
day: '19'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1016/j.immuni.2020.04.020
external_id:
  isi:
  - '000535371100002'
  pmid:
  - '32433942'
intvolume: '        52'
isi: 1
issue: '5'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1016/j.immuni.2020.04.020
month: '05'
oa: 1
oa_version: Published Version
page: 721-723
pmid: 1
publication: Immunity
publication_identifier:
  eissn:
  - 1097-4180
  issn:
  - 1074-7613
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'T cells: Bridge-and-channel commute to the white pulp'
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 52
year: '2020'
...