The B-cell function in patients with chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is characterized by the proliferation of dysfunctional B cells, resulting in significant immune dysregulation. Patients with CLL exhibit varied responses to B-cell receptor (BCR) targeted therapies, emphasizing the need for tailored immunotherapy approaches. This study investigated B cell function in untreated patients with CLL, and we further explored the effects of ex vivo protein kinase C activation on immune checkpoint expression and B cell profiles. Peripheral blood samples were collected from 21 untreated patients with CLL at King Edward Hospital in South Africa, between 2019 and 2022. B cells were stimulated with phorbol myristate acetate (PMA) and ionomycin. Using flow cytometry, the study explored the levels of B cell subsets and immune checkpoint proteins programmed cell death-ligand 2 (PD-L2) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) expression on various B cell subsets. PMA and ionomycin B cell stimulation upregulated CTLA-4 and PD-L2 expression on B cell subsets (p<0.0001). As expected, monoclonal antibodies targeting PD-1, PD-L1 and CTLA-4 significantly downregulated the CTLA-4 expression of B cell subsets (p<0.05), while PD-L2 exhibited varied responses in different B cell subsets. In addition, these monoclonal antibodies increased the levels of memory B cells (p<0.0128) and activated memory B cells (p<0.01). Protein kinase C activation on B cells stimulates immune checkpoint expression. The use of monoclonal antibodies on B cells play a critical role in the B cell function through the reduction of CD38 expressing activated B cells and upregulation of memory B cells. Moreover, the monoclonal antibody targeting PD-1, PD-L1 and CTLA-4 are effective in reducing the expression of CTLA-4 on B cell subsets.