The course of disease in patients suffering from chronic lymphocytic leukem
ia (CLL) is determined by a profound dysregulation of the immune system. Th
e resulting immune suppression is the main cause of death in those patients
. In the present study we addressed the question of whether leukemic B cell
s (B-CLL) are able to suppress regular T cell/B cell interaction. Activated
CD4(+)T cell clones induce expression of the early activation antigen CD23
on B lymphocytes in vitro Under conditions used, this B cell activation ev
ent was dependent upon direct T cell contact. Addition of certain bystander
B-CLL cells or normal B lymphocytes resulted in a cell number-dependent in
hibition of B cell induction. This seems to reflect the competition of B-CL
L cells for a cell contact-mediated T cell helper signal. By using CD40 lig
and transfected fibroblasts as a substitute for T cell help, we show that t
he same B-CLL cells also suppress CD40 ligand-mediated B cell activation. B
-CLL cells differ in their ability to inhibit CD40 ligand-mediated B cell a
ctivation. Some B-CLL cases (eight out of 14) are unable to compete for the
T cell or CD40 ligand-mediated signal, even though they can functionally i
nteract with CD40 ligand and thereby get activated themselves. In addition,
these results indicate that the observed inhibition is not a result of cel
l crowding by merely reducing the chance of specific B cell/T cell interact
ions. Collectively, these data indicate that B-CLL cells are able to inhibi
t the interaction of activated T lymphocytes with normal B lymphocytes in v
itro. Perturbed T cell/B cell interaction may represent an important mechan
ism underlying the various defects of the specific immune system observed i
n patients suffering from B-CLL.