C‐fms protein expression by B‐cells, with particular reference to the hairy cells of hairy‐cell leukaemia

Although the hairy cells (HCs) of hairy cell leukaemia (HCL) are now thought to be a form of activated B cell, they have long been known to possess certain monocytoid characteristics. Since the proto‐oncogene c‐fms is a feature of cells of the monocyte/macrophage lineage, we examined HCs for c‐fms expression. We found that approximately 80% of peripheral blood HCs expressed the c‐fms protein (8/8 cases). Expression of the 150 kD protein by HCs was shown using three different techniques, APAAP, immunofluorescence and immunoprecipitation, using two different antibodies. Other mature B cell lymphoproliferative disorders examined (PLL, CLL and multiple myeloma) did not express c‐fms. We also examined the c‐fms expression of normal B‐cells: both the in vivo activated (low density) fraction of tonsil B cells and tonsil B cells activated in vitro with SAC plus IL‐2 expressed the c‐fms protein. As in the case of monocytes c‐fms expression by HCs was shown to be down regulated by its ligand M‐CSF, and by TNFα, both caused a decrease in the receptor expression from 80% to 30% and in the intensity of staining from 6 to 3 x 10 4 molecules/cell. However, as for monocytes, GM‐CSF treatment of HCs had no effect on the expression of c‐fms: αIFN also had no effect. M‐CSF treatment of HCs also induced phosphorylation of c‐fms, and a number of other proteins, on tyrosine. However, M‐CSF was unable to induce HC proliferation either alone or in combination with IL‐2, IL‐4 or IL‐6; in addition it had no effect on HC proliferation induced by SAC, anti‐μ or TNFα. In addition, M‐CSF either alone, or in combination with the above cytokines, had no effect on the differentiated state of HCs as shown by both immunoglobulin secretion and surface antigen expression. M‐CSF also had no effect on the morphology or long‐term survival of HCs in culture. This study therefore demonstrates that both HCs and activated B‐cells express c‐fms, and that M‐CSF and binds to and activates its receptor on HCs. Although c‐fms and several other proteins were shown to be phosphorylated in response to M‐CSF, the functional consequences of this phosphorylation remain unclear.