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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-cellreceptor to T-helper cells via major histocompatibility complex (MHC) class II, antigens recognized by someCLL cells may be encountered in a particulate form. Here the ability of CLL cells to internalize and presentanti-immunoglobulin M (IgM) beads as a model for the interaction of CLL cells with particulate antigenswas investigated.Methods: The effect of anti-IgM beads on antigen presentation pathways was analyzed using RNA-seq andinternalization of anti-IgM beads by primary CLL cells was investigated using confocal microscopy and flowcytometry. Antigen presentation was investigated by analyzing activation of a T-cell line expressing a T-cellreceptor specific for a peptide derived from mouse κ light chains after incubating CLL cells with a mouseκ light chain-containing anti-IgM monoclonal antibody. Kinase inhibitors were used to characterize thepathways mediating internalization and antigen presentation.Results: Stimulation of surface IgM of CLL cells increased expression of the antigen presentation machineryand CLL cells were able to phagocytose anti-IgM beads. Internalization of anti-IgM beads was associatedwith MHC class II-restricted activation of cognate T-helper cells. Antigen presentation by CLL cells wasdependent on activity of spleen tyrosine kinase (SYK) and phosphatidylinositol 3-kinase delta (PI3Kδ) butwas 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 cellsmay be particularly important for recruitment of T-cell help in vivo in response to particulate antigens.

B-cell receptor dependent phagocytosis and presentation of particulate antigen by chronic lymphocytic leukemia cells