B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes.
B-cell chronic lymphocytic leukemia (B-CLL) is considered an accumulative disease of antigen-naive CD5(+) B lymphocytes that circulate in the resting state. However, to evaluate the possibility that B-CLL cells resemble antigen-experienced and activated B cells, we analyzed the expression of markers of cellular activation and differentiation on CD5(+)CD19(+) cells from B-CLL patients and from age-matched healthy donors. The leukemic cells from all B-CLL patients, including those that lack significant numbers of V gene mutations, bear the phenotype of activated B cells based on the overexpression of the activation markers CD23, CD25, CD69, and CD71 and the underexpression of CD22, Fcgamma receptor IIb, CD79b, and immunoglobulin D that are down-regulated by cell triggering and activation. Furthermore, these leukemic cells resemble antigen-experienced lymphocytes in the underexpression of molecules that are down-regulated by cell triggering and in the uniform expression of CD27, an identifier of memory B cells. A comparison of the phenotypes of B-CLL patients with and without immunoglobulin V gene mutations suggests that the 2 subgroups differ both in specific marker expression (CD69, CD71, CD62 L, CD40, CD39, and HLA-DR) and in the time since antigenic stimulation, based on the reciprocal relationship of CD69 and CD71 expression. These findings imply that the leukemic cells from all B-CLL cases (irrespective of V gene mutations) exhibit features of activated and of antigen-experienced B lymphocytes and that the B-CLL cells that differ in immunoglobulin V genotype may have different antigen-encounter histories.
Damle
Rajendra N
RN
North Shore-Long Island Jewish Research Institute, Manhasset, NY 11030, USA.
Ghiotto
Fabio
F
Valetto
Angelo
A
Albesiano
Emilia
E
Fais
Franco
F
Yan
Xiao-Jie
XJ
Sison
Cristina P
CP
Allen
Steven L
SL
Kolitz
Jonathan
J
Schulman
Philip
P
Vinciguerra
Vincent P
VP
Budde
Petra
P
Frey
Jurgen
J
Rai
Kanti R
KR
Ferrarini
Manlio
M
Chiorazzi
Nicholas
N
D015703:Antigens, CD / Q000032:analysis*; D001402:B-Lymphocytes / Q000276:immunology*; D018955:CD36 Antigens; D018956:CD5 Antigens / Q000032:analysis; D002462:Cell Membrane / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D008213:Lymphocyte Activation; D012016:Reference Values; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018955:CD36 Antigens; D018956:CD5 Antigens