TY - JOUR
T1 - B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes
AU - Damle, Rajendra N.
AU - Ghiotto, Fabio
AU - Valetto, Angelo
AU - Albesiano, Emilia
AU - Fais, Franco
AU - Yan, Xiao Jie
AU - Sison, Cristina P.
AU - Allen, Steven L.
AU - Kolitz, Jonathan
AU - Schulman, Philip
AU - Vinciguerra, Vincent P.
AU - Budde, Petra
AU - Frey, Jurgen
AU - Rai, Kanti R.
AU - Ferrarini, Manlio
AU - Chiorazzi, Nicholas
PY - 2002/6/1
Y1 - 2002/6/1
N2 - 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, Fcγ 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.
AB - 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, Fcγ 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.
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U2 - 10.1182/blood.V99.11.4087
DO - 10.1182/blood.V99.11.4087
M3 - Article
C2 - 12010811
AN - SCOPUS:0036624881
VL - 99
SP - 4087
EP - 4093
JO - Blood
JF - Blood
SN - 0006-4971
IS - 11
ER -