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Expression of CD27 and its ligand, CD70, on chronic lymphocytic leukemia B
cells
EA Ranheim, MJ Cantwell and TJ Kipps
Department of Medicine, University of California San Diego, La Jolla
92093-0663, USA.
Crosslinking the CD27 antigen on T cells provides a costimulatory signal
that, in concert with T-cell receptor crosslinking, can induce T- cell
proliferation and cellular immune activation. We find that chronic
lymphocytic leukemia (CLL) B cells from most patients coexpress both
membrane-bound and soluble CD27, along with its newly identified ligand,
CD70. The expression of soluble CD27 may preclude leukemic B cells from
stimulating T cells via CD70, thereby potentially impairing their ability
to function as effective antigen-presenting cells. We find that leukemic
B-cell expression of soluble and membrane-bound CD27 can be downmodulated
through a CD40-dependent signal. This signal also induces enhanced
expression of CD70 on both normal and leukemic B cells. We find that tumor
necrosis factor (TNF)-alpha, or the Th1 cytokine interferon (IFN)-gamma,
also can induce downmodulation of CD27, whereas Th2-associated cytokines
interleukin-4 (IL-4) or IL-10 can enhance leukemic B-cell expression of
this accessory molecule. The modulation of CD27 induced by these conditions
is accompanied by reciprocal changes in the expression levels of CD70,
suggesting that these accessory molecules may be engaged in reciprocal
receptor-ligand downmodulation. Consistent with this, we observe that
co-culture of CLL B cells with transfected murine plasmacytoma cells that
express human CD70 affects downmodulation of CD27 and enhanced expression
of CD70 on leukemic B cells, but does not affect expression of CD27 mRNA.
However, we find that CD40-crosslinking, in addition to reducing the level
of CD27 protein, also reduces leukemic B-cell expression of CD27 mRNA. This
argues that the changes in the expression levels of CD27 following
CD40-signaling are not simply due to induced increases in the expression
levels of CD70. Finally, we demonstrate that reciprocal changes in
expression of CD27 and CD70 may contribute to the enhanced
antigen-presenting capacity of CLL B cells after CD40-dependent leukemic
B-cell activation. These findings expand the understanding of the
regulation of costimulatory molecules important in antigen presentation and
also have implications for the immunobiology of and therapy for CLL.
Volume 85,
Issue 12,
pp. 3556-3565,
06/15/1995
Copyright © 1995 by The American Society of Hematology
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