ZAP-70 is expressed by a subset of normal human B-lymphocytes displaying an activated phenotype.
The Syk family tyrosine kinase ZAP-70 is essential for normal T-cell development and signaling. Recently, leukemic cells from some patients with B-cell chronic lymphocytic leukemia (B-CLL) were shown to express ZAP-70. Owing to the prognostic value of B-CLL ZAP-70 expression, this phenotype may reflect intrinsic biological differences between the two subsets of disease. However, it remains unclear whether CLL-B cells aberrantly acquire ZAP-70 expression during the transformation process or whether ZAP-70 may be expressed under certain conditions in normal human B-lymphocytes. To discriminate between these two possibilities, we assessed ZAP-70 expression in normal human B-lymphocytes. Our data demonstrate that ZAP-70 is expressed in a subpopulation of tonsillar and splenic normal B-lymphocytes that express an activated phenotype. Furthermore, ZAP-70 expression can be induced in vitro upon stimulation of blood and tonsillar B cells. Finally, we show that phosphorylation of ZAP-70 occurs in tonsillar B cells with stimulation through the B-cell receptor. These results provide new insight into normal human B-cell biology as well as provide clues about the transformed cell in B-CLL.
Nolz
J C
JC
Department of Immunology, Mayo Clinic College of Medicine, Mayo Graduate School, Rochester, MN 55905, USA.
Tschumper
R C
RC
Pittner
B T
BT
Darce
J R
JR
Kay
N E
NE
Jelinek
D F
DF
D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000502:physiology*; D014066:Palatine Tonsil / Q000166:cytology; D010641:Phenotype; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D014162:Transfection; D051746:ZAP-70 Protein-Tyrosine Kinase
D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human