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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