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

Abstract

SUMMARYIt has previously been reported that the expression of Ihe complement receptors CR I (CD35) and CR2 (CD21) on malignant B cells in CLL is reduced compared with the expression on normal B cells, while deposition of eoniplenient C3 fragments, as a consequence ofalternative pathway (AP) activation of complement, is observed on mononuclear cells from patients with B CLL. Following our demonstration that normal B cells are capable of activating the AP of complement in a CR2-dependent fashion, we have chosen to re-examine the complement-activating ability of B CLL cells in relation to their altered phenotype with respect to CR2 and the complement regulatory membrane proteins. CRl. decay accelerating factor (DAF) (CD55) and membrane cofactor protein (MCP) (CD46). Flow cytometry was used to measure expression of complement receptors and regulatory proteins on CDS*" B cells from CLL patients, as well as the deposition of C3 fragments occurring both in vivo and after in vitro AP activation. We have confirmed the reduced expression of CRl and CR2 on CLL cells and have shown that AP activation in the presence of homologous, normal serum was reduced on B CLL cells compared with normal B cells. The degree of AP activation correlated directly with CR2 expression. In addition, we observed that CLL cells bear in v/ro-deposited C3d.g. although at a significantly lower level than normal B cells.

Infectious Complications of Chronic Lymphocytic Leukemia

“…26 Another group demonstrated reduced expression of complement receptors CR1 and CR2 on B-CLL cells, as well as decreased activation of the alternate complement pathway, but it is unclear if these translate into an increased risk of infection. 27…”

Sepsis due to Erysipelothrix rhusiopathiae in a Patient with Chronic Lymphocytic Leukemia Associated with Bronchopneumonia due to PSeudomonas aeruginosa And Escherichia coli: A Case Report

“…CLL is associated with a greater susceptibility to infections due to multiple mechanisms: immunosuppression due to the primary disease, association with a deficit of cellular-mediated immunity through intrinsic deficiencies or consequent to immunosuppressive therapy ( 11 ) (eg, the functional deficit of the T helper cells [12]), an increased activity of T suppressor cells or an inverted CD4/CD8 ratio ( 13 ) combined with hypogammaglobulinemia. Deficiency in the complement system also plays an important role in the development of infections due to encapsulated organisms in patients with advanced-stage CLL, along with the decrease in expression of the complement receptors at the level of the B-cell CLL cells (the CR1 and CR2 receptors) and the reduction of the alternative pathway of the complement system ( 14 ). The risk for infection in patients with CLL is associated with neutropenia following a progressive bone marrow invasion and immunosuppressive chemotherapy, and also with the decrease in chemotaxis induced by the complement fragment C5a.…”

The versatile functions of complement C3‐derived ligands

“…This finding might have an important relevance in vivo, as both virus-infected and tumor cells are known to fix C3b. [19][20][21][22] Therefore, C3b-coated exosomes released by these cells might contribute to the immune response in pathologic conditions, particularly when the antigen stimulus is low.…”

“…Autologous cells normally are protected by the regulatory molecules from C3b‐fixation which may lead to complement‐dependent lysis. Nevertheless, deposition of C3b onto the surface of nucleated cells can occur not only in pathologic conditions, like in the case of malignantly transformed cells and virus‐infected cells, but also in physiological conditions and in the case of the monocytic human cell line U937 . Furthermore, Matsumoto and Seya demonstrated C3 deposition and homotypic cell adhesion in the case of P39, a human myeloid cell line.…”