Differences in constitutive and activation-induced expression of CD69 and CD95 between normal and chronic lymphocytic leukemia B cells.
B-cell chronic lymphocytic leukemia (B-CLL) is characterized by a sustained accumulation of long-lived and well-differentiated B lymphocytes in lymphoid tissues, peripheral blood and bone marrow. Although the pathogenesis of this disease is not entirely understood, altered apoptosis is believed to play a relevant role in B-CLL. In this study, we compared the expression of CD95, the best characterized surface molecule involved in triggering the apoptotic machinery, on normal and CLL B cells before and after in vitro activation with polyclonal stimulators. Cell activation was monitored by verifying the induced expression of the early activation antigen CD69. Freshly analyzed CLL B cells showed significantly lower levels of CD95 than normal B cells. Moreover, following in vitro culture with phorbol 12-myristate 13-acetate (PMA) + ionomycin, phytohemagglutinin, or pokeweed mitogen, CLL B cells failed to upregulate CD95 expression as efficiently as normal B cells. Impairment of CD95 upregulation was mainly observed following PMA + ionomycin treatment. In contrast, CLL B cells were shown to express CD69 as well as normal B cells, regardless of the activator used, indicating that CLL B cells retain the ability to respond to activating stimuli but are unable to efficiently implement the CD95-mediated activation-induced cell death (AICD) program. In conclusion, these results suggest that prolonged survival of CLL B cells may be contributed to by alterations in AICD mechanisms.
De Fanis
Umberto
U
Division of Internal Medicine and Immunoallergology, Department of Gerontology, Geriatrics and Metabolic Diseases, The Second University of Naples School of Medicine, Piazza Luigi Miraglia 3, I-80138 Naples, Italy.
Romano
Ciro
C
Dalla Mora
Liliana
L
Sellitto
Ausilia
A
Guastafierro
Salvatore
S
Tirelli
Angelo
A
Bresciano
Elio
E
Giunta
Riccardo
R
Lucivero
Giacomo
G
D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002273:Carcinogens / Q000494:pharmacology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D037181:Lectins, C-Type; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D011043:Pokeweed Mitogens / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D002273:Carcinogens; D015759:Ionomycin; D007476:Ionophores; D037181:Lectins, C-Type; D010835:Phytohemagglutinins; D011043:Pokeweed Mitogens; D013755:Tetradecanoylphorbol Acetate; D019014:fas Receptor; D000099192:CD69 Antigens