B-cell receptor dependent phagocytosis and presentation of particulate antigen by chronic lymphocytic leukemia cells
B-cell receptor dependent phagocytosis and presentation of particulate antigen by chronic lymphocytic leukemia cells
Aim: T-helper cells could play an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), a common B-cell neoplasm. Although CLL cells can present soluble antigens targeted from the B-cell receptor to T-helper cells via major histocompatibility complex (MHC) class II, antigens recognized by some CLL cells may be encountered in a particulate form. Here the ability of CLL cells to internalize and present anti-immunoglobulin M (IgM) beads as a model for the interaction of CLL cells with particulate antigens was investigated.
Methods: The effect of anti-IgM beads on antigen presentation pathways was analyzed using RNA-seq and internalization of anti-IgM beads by primary CLL cells was investigated using confocal microscopy and flow cytometry. Antigen presentation was investigated by analyzing activation of a T-cell line expressing a T-cell receptor specific for a peptide derived from mouse κ light chains after incubating CLL cells with a mouse κ light chain-containing anti-IgM monoclonal antibody. Kinase inhibitors were used to characterize the pathways mediating internalization and antigen presentation.
Results: Stimulation of surface IgM of CLL cells increased expression of the antigen presentation machinery and CLL cells were able to phagocytose anti-IgM beads. Internalization of anti-IgM beads was associated with MHC class II-restricted activation of cognate T-helper cells. Antigen presentation by CLL cells was dependent on activity of spleen tyrosine kinase (SYK) and phosphatidylinositol 3-kinase delta (PI3Kδ) but was unaffected by inhibitors of Bruton’s tyrosine kinase (BTK).
Conclusions: CLL cells can internalize and present antigen from anti-IgM beads. This capacity of CLL cells may be particularly important for recruitment of T-cell help in vivo in response to particulate antigens.
B-cell receptor, Chronic lymphocytic leukemia, T helper cell, antigen presentation, human leukocyte antigen class II, major histocompatibility complex class II, phagocytosis
37-49
Minton, Annabel Rachel
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Smith, Lindsay D.
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Bryant, Dean J.
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Strefford, Jonathan
3782b392-f080-42bf-bdca-8aa5d6ca532f
Forconi, Francesco
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Stevenson, Freda
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Tumbarello, David
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James, Edd
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Løset, Geir Åge
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Munthe, Ludvig A.
ac7791c2-fc31-45df-94ee-c0403a7be28b
Steele, Andrew J.
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Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
25 February 2022
Minton, Annabel Rachel
c5daea3a-7a9a-427c-8200-122726ce58fc
Smith, Lindsay D.
1d44c2d0-d5af-411e-b6cd-9b5633f2eb1e
Bryant, Dean J.
48cd72a4-b658-4548-9752-c93a3f767390
Strefford, Jonathan
3782b392-f080-42bf-bdca-8aa5d6ca532f
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Stevenson, Freda
ba803747-c0ac-409f-a9c2-b61fde009f8c
Tumbarello, David
75c6932e-fdbf-4d3c-bb4f-48fbbdba93a2
James, Edd
a7c63dd2-243d-4121-b553-e3e072843e03
Løset, Geir Åge
8b1b7ac0-0c93-4132-8c00-7322b61ef975
Munthe, Ludvig A.
ac7791c2-fc31-45df-94ee-c0403a7be28b
Steele, Andrew J.
526a311f-43d0-4840-9661-88d6c7ddd3e8
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Minton, Annabel Rachel, Smith, Lindsay D., Bryant, Dean J., Strefford, Jonathan, Forconi, Francesco, Stevenson, Freda, Tumbarello, David, James, Edd, Løset, Geir Åge, Munthe, Ludvig A., Steele, Andrew J. and Packham, Graham
(2022)
B-cell receptor dependent phagocytosis and presentation of particulate antigen by chronic lymphocytic leukemia cells.
Exploration of Targeted Anti-Tumor Therapy, 3 (1), .
(doi:10.37349/etat.2022.00070).
Abstract
Aim: T-helper cells could play an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), a common B-cell neoplasm. Although CLL cells can present soluble antigens targeted from the B-cell receptor to T-helper cells via major histocompatibility complex (MHC) class II, antigens recognized by some CLL cells may be encountered in a particulate form. Here the ability of CLL cells to internalize and present anti-immunoglobulin M (IgM) beads as a model for the interaction of CLL cells with particulate antigens was investigated.
Methods: The effect of anti-IgM beads on antigen presentation pathways was analyzed using RNA-seq and internalization of anti-IgM beads by primary CLL cells was investigated using confocal microscopy and flow cytometry. Antigen presentation was investigated by analyzing activation of a T-cell line expressing a T-cell receptor specific for a peptide derived from mouse κ light chains after incubating CLL cells with a mouse κ light chain-containing anti-IgM monoclonal antibody. Kinase inhibitors were used to characterize the pathways mediating internalization and antigen presentation.
Results: Stimulation of surface IgM of CLL cells increased expression of the antigen presentation machinery and CLL cells were able to phagocytose anti-IgM beads. Internalization of anti-IgM beads was associated with MHC class II-restricted activation of cognate T-helper cells. Antigen presentation by CLL cells was dependent on activity of spleen tyrosine kinase (SYK) and phosphatidylinositol 3-kinase delta (PI3Kδ) but was unaffected by inhibitors of Bruton’s tyrosine kinase (BTK).
Conclusions: CLL cells can internalize and present antigen from anti-IgM beads. This capacity of CLL cells may be particularly important for recruitment of T-cell help in vivo in response to particulate antigens.
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Accepted/In Press date: 28 January 2022
Published date: 25 February 2022
Additional Information:
Funding Information:
This study was supported by Cancer Research UK (C2750/A23669), the Southampton Experimental Cancer Medicine and Cancer Research Centres (C24563/A15581, C34999/A18087), the University of Southampton and the Medical Research Council. These sponsors had no input into any aspect of the study.
Publisher Copyright:
© The Author(s) 2022.
Keywords:
B-cell receptor, Chronic lymphocytic leukemia, T helper cell, antigen presentation, human leukocyte antigen class II, major histocompatibility complex class II, phagocytosis
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Local EPrints ID: 472532
URI: http://eprints.soton.ac.uk/id/eprint/472532
ISSN: 2692-3114
PURE UUID: 5be20dd7-2d8c-4381-8b2c-07e74782c757
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Date deposited: 07 Dec 2022 17:59
Last modified: 17 Mar 2024 03:35
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Author:
Annabel Rachel Minton
Author:
Lindsay D. Smith
Author:
Dean J. Bryant
Author:
Edd James
Author:
Geir Åge Løset
Author:
Ludvig A. Munthe
Author:
Andrew J. Steele
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