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Jeremy S. Abramson, MD, MMSc
Jeremy S. Abramson, MD, MMSc
Posted: Wednesday, April 13, 2022
According to findings presented in the journal Exploration of Targeted Anti-tumor Therapy, chronic lymphocytic leukemia (CLL) cells may internalize and present antigen from anti-immunoglobulin M beads, demonstrating that mutated and unmutated CLL cells can use their C-cell receptors to present particulate antigens. The ability of CLL cells to do so may shed light on pathogenesis, especially since some CLL B-cell receptors can recognize antigen and autoantigens, concluded Graham Packham, PhD, of the University of Southampton, United Kingdom, and colleagues.
“[Antigen] presentation appears to be relatively independent of BTK [Bruton’s tyrosine kinase] and may therefore be unaffected in patients treated with ibrutinib or other [Bruton’s tyrosine kinase] inhibitors,” the authors said.
The authors used RNA sequencing to investigate anti-immunoglobulin M beads on antigen presentation pathways; they employed confocal microscopy and flow cytometry to explore the internalization of anti-immunoglobulin M beads by primary CLL cells. Antigen presentation was inspected by analyzing the 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-immunoglobulin M monoclonal antibody.
By stimulating surface anti-immunoglobulin M of CLL cells, the authors found an increased expression of the antigen presentation machinery. Additionally, CLL cells were able to phagocytose anti-immunoglobulin M beads. The internalization of anti-immunoglobulin beads was associated with major histocompatibility complex class II–restricted activation of cognate T-helper cells. In addition, antigen presentation by CLL cells appeared to be dependent on the activity of spleen tyrosine kinase and phosphatidylinositol 3-kinase delta but was unaffected by inhibitors of BTK.
Disclosure: The authors reported no conflicts of interest.
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