@article{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.},
author = {Minton, Annabel R and Smith, Lindsay D and Bryant, Dean J and Strefford, Jonathan C and Forconi, Francesco and Stevenson, Freda K and Tumbarello, David A and James, Edd and Løset, Geir Åge and Munthe, Ludvig A and Steele, Andrew J and Packham, Graham},
doi = {10.37349/etat.2022.00070},
journal = {Exploration of Targeted Anti-tumor Therapy},
pages = {37--49},
title = {{B-cell receptor dependent phagocytosis and presentation of particulate antigen by chronic lymphocytic leukemia cells}},
url = {https://www.explorationpub.com/Journals/etat/Article/100270},
volume = {3}
year = {2022},
number = {1}
}