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Blood, 1 June 2002, Vol. 99, No. 11, pp. 4087-4093
NEOPLASIA
B-cell chronic lymphocytic leukemia cells express a surface
membrane phenotype of activated, antigen-experienced B
lymphocytes
Rajendra N. Damle,
Fabio Ghiotto,
Angelo Valetto,
Emilia Albesiano,
Franco Fais,
Xiao-Jie Yan,
Cristina P. Sison,
Steven L. Allen,
Jonathan Kolitz,
Philip Schulman,
Vincent P. Vinciguerra,
Petra Budde,
Jurgen Frey,
Kanti R. Rai,
Manlio Ferrarini, and
Nicholas Chiorazzi
From the North Shore-Long Island Jewish Research
Institute; the Department of Medicine, North Shore University Hospital;
and the Department of Medicine, New York University School of Medicine,
Manhasset, NY; Facultät für Chemie-Biochemi II,
Universität Bielefeld, Germany; the Department of Medicine, Long
Island Jewish Medical Center, and the Department of Medicine, Albert
Einstein College of Medicine, New Hyde Park, NY; and the Division of
Clinical Immunology, Istituto Nazionale per la Ricerca sul Cancro,
Dipartmento Oncologia Clinica e Sperimentale Universita di Genova,
Genoa, Italy.
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, Fc
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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