B lymphocytes in humans express ZAP-70 when activated in vivo.
ZAP-70 is a protein tyrosine kinase initially found in T and NK cells. Recently, this important signaling element was detected in leukemic B cells from a subgroup of patients with B cell chronic lymphocytic leukemia (B-CLL). In this study, ZAP-70 was detected in normal B cells from human tonsils, but not from peripheral blood. The cDNA sequence of B cell ZAP-70 was the same as that in T cells. Germinal center B cells and plasma cells had a substantial proportion of ZAP-70+ cells, while memory and follicular mantle B cells, which contain low numbers of activated B cells, expressed relatively little ZAP-70. A cell fraction of IgD+, CD38+ B cells, which are comprised of many in vivo activated B cells, exhibited the highest levels of ZAP-70. Density gradient fractionation of tonsil B cells confirmed that ZAP-70 was not expressed by resting B cells, but was expressed by buoyant, in vivo activated B cells. In these B cells, the expression of ZAP-70 correlated with that of CD38 and not with that of CD5, a hallmark of B-CLL cells. B-CLL cells are activated cells and their ZAP-70 expression reflects a normal property of activated B cells populations rather than a neoplastic aberration.
Division of Medical Oncology C, Istituto Nazionale per la Ricerca sul Cancro, IST, Genova, Italy. giovanna.cutrona@istge.it
Giovanna
G
Cutrona
Monica
M
Colombo
Serena
S
Matis
Daniele
D
Reverberi
Mariella
M
Dono
Vincenzo
V
Tarantino
Nicholas
N
Chiorazzi
Manlio
M
Ferrarini
D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D018956:CD5 Antigens / Q000276:immunology; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology*; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D006801:Humans; D007072:Immunoglobulin D / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis / Q000276:immunology*
D018956:CD5 Antigens; D007072:Immunoglobulin D; D008562:Membrane Glycoproteins; D051746:ZAP-70 Protein-Tyrosine Kinase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1