We studied a variant CD5-
B cell chronic lymphocytic leukemia (CLL) cell population that produces pathologic
IgM kappa
rheumatoid factor autoantibodies. In contrast to common CD5+ B cell CLL, this variant
leukemia cell population displays intraclonal diversity in its expressed Ig V genes, similar to that noted for follicular B cell non-Hodgkin's
lymphomas. Also, in contrast to common B cell CLL, these
leukemia cells rapidly undergo cell death hours after being placed in tissue culture. We find that addition of Ag (aggregated human
IgG) enhances significantly the survival of these cells in vitro.
Leukemia cell survival also could be enhanced by exogenous IFN-gamma or anti-CD40 presented on
Fc gamma RII (CDw32)-expressing L cells, but not by exogenous
IL-4,
IL-6, or monomeric human
IgG. We find that Ag acts directly on the
leukemia B cells to inhibit apoptosis. This effect could be mimicked by cross-linking the
leukemia cells' surface
IgM receptors with immobilized murine mAb specific for human
Ig mu-chains, but not by immobilized mAb of irrelevant specificity. In contrast to most follicular NHL, this
leukemia B cell population does not have evidence of bcl-2 gene rearrangement. Also, in contrast to non-Hodgkin's
lymphomas and most B cell CLL, these cells do not express detectable amounts of bcl-2. Finally, although capable of inhibiting apoptosis, surface Ig receptor cross-linking does not induce expression of bcl-2 in these variant
leukemia cells. We hypothesize that the lack of bcl-2 expression may render these
leukemia cells particularly dependent upon the survival signal(s) derived from surface Ig receptor cross-linking. This state may represent an early stage in
leukemia/lymphomagenesis, possibly accounting for the intraclonal diversity observed in the Ig V genes expressed by certain CD5-
B cell leukemias and
lymphomas.