ZAP-70 is expressed by normal and malignant human B-cell subsets of different maturational stage.
ZAP-70 tyrosine kinase is involved in signalling pathways following T-cell receptor stimulation and was originally described only in T cells and natural killer cells. ZAP-70 expression has been reported in normal mouse B lineage cells and in human malignant B lymphocytes, mainly in chronic lymphocytic leukemia (CLL) where it correlates with clinical outcome. We analyzed several B-cell lines and ex vivo malignant B cells, ranging from acute lymphoblastic leukemia to multiple myeloma and reflecting different stages of B-cell differentiation, and they showed ZAP-70 expression regardless their maturation stage. We then analyzed by Western blot and flow cytometry different human normal B-lymphocyte subpopulations: naïve, germinal center and memory B cells from tonsils, CD19+ CD5+ cells from cord blood and CD19+ lymphocytes from peripheral blood. All expressed ZAP-70 protein, though at different levels depending on their differentiation, activation and tissue localization. In addition, ZAP-70 expression levels could be modulated following stimulation via the B-cell receptor. These findings implicate a potential role of ZAP-70 in the signalling pathway of B lymphocytes at different maturational stages, indicate that ZAP-70 expression is not a CLL-specific feature among B-cell malignancies and suggest that the absence of ZAP-70 rather than its presence should be considered abnormal for malignant B lymphocytes.
Department of Oncology, Università Vita Salute - San Raffaele, Milan, Italy.
C
C
Scielzo
A
A
Camporeale
M
M
Geuna
M
M
Alessio
A
A
Poggi
M R
MR
Zocchi
M
M
Chilosi
F
F
Caligaris-Cappio
P
P
Ghia
D015703:Antigens, CD / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism*; D015153:Blotting, Western; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism* / Q000473:pathology; D012680:Sensitivity and Specificity; D015398:Signal Transduction; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis* / Q000235:genetics*
D015703:Antigens, CD; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human