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Chronic Lymphocytic Leukemia B Cells Can Express CD40
Ligand and Demonstrate T-Cell Type Costimulatory Capacity
Elaine J. Schattner,
John Mascarenhas,
Inna Reyfman,
Mary Koshy,
Caroline Woo,
Steven M. Friedman, and
Mary K. Crow
From the Division of Hematology-Oncology, Department of Medicine, The
New York Hospital-Cornell Medical Center, New York, NY; and the
Division of Rheumatology, The Hospital for Special Surgery, New York,
NY.
Chronic lymphocytic leukemia (CLL) is characterized by a clonal
expansion of CD5+ B cells in the peripheral blood.
Associated immune aberrations include abnormal Th-cell
function and pathogenic autoantibodies. Under most circumstances, CLL B
cells do not proliferate in culture and express a limited repertoire of
surface antigens, including CD19, CD20, CD23, CD27, CD40, and CD70. In
this report, we demonstrate that freshly isolated B cells from a subset
of CLL cases constitutively express CD40 ligand (CD40L, CD154), a
member of the tumor necrosis factor family which is normally expressed
by activated CD4+ T cells and mediates T-cell-dependent
B-cell proliferation and antibody production. The degree of CD40L
expression varied considerably among the CLL cases examined. CD40L was
detected in purified CLL B cells by immunofluorescence flow cytometry,
by RT-PCR, and by immunoprecipitation. To demonstrate that CD40L in the
CLL B cells is functional, we used irradiated CLL cells to stimulate
IgG production by target, nonmalignant B cells in coculture. The CLL B
cells induced IgG production by normal B cells to a similar degree as did purified T cells in a process which was partially inhibited by
monoclonal antibody to CD40L. This is one of the first reports of CD40L
expression in a B-cell tumor. The data suggest that CD40L in the tumor
cells may be a factor in the generation of pathologic antibodies by
normal B cells in some patients with CLL.
Blood, Vol. 91 No. 8 (April 15), 1998:
pp. 2689-2697
© 1998 by The American Society of Hematology.
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