Role of B-cell antigen receptor-associated molecules and lipid rafts in CD5-induced apoptosis of B CLL cells

• Published in: Leukemia Vol. 19; no. 2; pp. 223 - 229
• Main Authors: RENAUDINEAU, Y, NEDELLEC, S, BERTHOU, C, LYDYARD, P. M, YOUINOU, P, PERS, J-O
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01-02-2005; Nature Publishing Group
• Subjects: Abnormalities; Antigens; Antigens, CD - genetics; Antigens, CD - immunology; Apoptosis; B-cell receptor; B-Lymphocytes - immunology; Biological and medical sciences; CD38 antigen; CD5 antigen; CD5 Antigens - immunology; CD79 Antigens; Cell Culture Techniques; Chronic lymphocytic leukemia; Crosslinking; Flow Cytometry; Hematologic and hematopoietic diseases; Humans; Immunoglobulin M; Immunology; Kinases; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - blood; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lipid rafts; Lipids; Lymphocytes B; Medical sciences; Membrane Microdomains - physiology; Phosphorylation; Rafts; Receptors, Antigen, B-Cell - physiology; Sheep; SHP-1 protein; Signal transduction; Signaling; Subgroups; Syk protein; Transcription, Genetic; Tyrosine; ZAP-70 protein; France; United States > US; lipid rafts; Lipid raft; Hematology; Malignant hemopathy; B-Lymphocyte; BCR; Chronic; Chronic lymphocytic leukemia; Cell death; CD5; Lymphoproliferative syndrome; B cell antigen receptor; Apoptosis
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2403601

A total of 40 patients with B-CLL were investigated for CD5-triggered apoptosis and categorized as 20 resistant (group I) and 20 sensitive patients (group II). The densities of surface IgM (sIgM) and CD5 were lower in group I than group II, as were the percentages of CD79b+, CD38+, and Zap70-expressing B cells. CD5 signaling was mediated through the BCR in group II B cells, as established by coimmunoprecipitation of CD5 and CD79a and tyrosine phosphorylation of CD79a. Following colocalization of CD5 and sIgM in membrane lipid rafts (LRs), Syk became associated with these molecules, whereas SHP-1 was uncoupled from CD5. Nonresponsiveness to CD5 cross-linking in group I was ascribed to three possible abnormalities, and defined as three subgroups of patients. In subgroups Ia and Ib, CD5 and sIgM colocalized within the LRs. SHP-1 remained attached to the BCR in subgroup Ia, but not in subgroup Ib, where signal transduction was associated with an excess of truncated CD79b. In subgroup Ic, CD5 and sIgM segregated into different LRs, resulting in no signaling of apoptosis.