Abstract
Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in the western world. In previous studies, various proportion of patients was found to carry CD11b+ or CD11c+ B cells whose presence was an unfavourable prognostic factor. The exact mechanism however, how these receptors contribute to the pathogenesis of CLL has not been revealed so far. Here we analysed the role of CD11b and CD11c on B cells of CLL patients in the adhesion to fibrinogen and in the migration towards stromal cell derived factor-1 (SDF-1) and studied the role of CR4 in the adherence of the CD11c+ B cell line BJAB. We observed that both CR3 and CR4 mediate adhesion of the malignant B cells. Moreover, we found, that CR4 was strongly involved in the migration of the leukemic cells towards the chemoattractant SDF-1. Our data suggest that CR3 and CR4 are not only passive markers on CLL B cells, but they might contribute to the progression of the disease. Since the role of SDF-1 is prominent in the migration of CLL cells into the bone marrow where their survival is supported, our findings help to understand how the presence of CD11c on leukemic B cells can worsen the prognosis of chronic lymphocytic leukaemia.
Highlights
The role of complement receptors CR3 (CD11b/CD18, known as Mac-1, αMβ2) and CR4 (CD11c/CD18, designated as p150,95; αXβ2) are known to be involved in actin linked functions such as phagocytosis, adhesion or migration
Since CD11b and CD11c are known to be expressed by various malignant B cells [4, 12,13,14,15,16,17,18,19], first we tested whether the cells of the EBV-negative Burkitt-like lymphoma line BJAB could serve as a model for examining the role of CR3 or CR4 expressed by malignant human B cells
Regarding their expression and role on B lymphocytes, we found recently that a proportion of B cells begin to express CD11c after BCR mediated activation, while CD11b could not be detected on B cells of healthy donors
Summary
The role of complement receptors CR3 (CD11b/CD18, known as Mac-1, αMβ2) and CR4 (CD11c/CD18, designated as p150,95; αXβ2) are known to be involved in actin linked functions such as phagocytosis, adhesion or migration. These two receptors of the β2-integrin family have earlier been suggested to mediate overlapping functions, we propose that they rather should be considered as “non-identical twins” [1], because of the functional segregation between them. Studying human monocytes, macrophages and dendritic cells. CLL B cells use CR3 and CR4 for adhesion while CR4 has a dominant role in migration. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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