Complement activation by malignant B cells from patients with chronic lymphocytic leukaemia (CLL)

Area of Science:

• Immunology
• Hematology
• Complement System Biology

Background:

• Malignant B cells in Chronic Lymphocytic Leukemia (CLL) exhibit reduced expression of complement receptors CR1 (CD35) and CR2 (CD21).
• Complement C3 fragments are found on mononuclear cells from CLL patients, indicating alternative pathway (AP) activation.
• Normal B cells activate the AP of complement in a CR2-dependent manner.

Purpose of the Study:

• To re-examine the complement-activating ability of B CLL cells.
• To investigate the relationship between altered phenotype (CR2, CR1, DAF, MCP) and complement activation in CLL.
• To compare in vivo and in vitro complement activation on CLL cells versus normal B cells.

Main Methods:

• Flow cytometry was employed to quantify complement receptors and regulatory proteins on CD5+ B cells from CLL patients.
• Measurement of C3 fragment deposition in vivo and after in vitro AP activation.
• Comparison of AP activation levels between CLL B cells and normal B cells using homologous serum.

Main Results:

• Reduced expression of CR1 and CR2 on CLL cells was confirmed.
• AP activation was significantly lower on B CLL cells compared to normal B cells.
• The extent of AP activation directly correlated with CR2 expression levels.
• CLL cells showed lower levels of in vivo-deposited C3d,g compared to normal B cells.

Conclusions:

• Reduced CR2 expression on CLL cells impairs their ability to activate the alternative pathway of complement.
• The findings provide insights into the altered complement interaction on malignant B cells in CLL.
• Therapeutic strategies targeting the complement system in CLL may need to consider these receptor-dependent activation differences.