Tumor Necrosis Factor Receptor Expression on Human Normal and Malignant B Lymphocytes: Anti-75-kDa Tumor Necrosis Factor Receptor Antibody Inhibits B-Cell Proliferation

Tumor necrosis factor (TNF) is a pleiotropic cytokine with broad regulatory functions in inflammation and the immune response [1, 2]. TNF also acts on B lymphocytes, it is thought to sustain the growth of Staphylococcus aureus Cowan strain 1 (SAC) stimulated B cells [3, 4]. Neoplastic B cells and activated B cells are able to secrete TNF and lymphotoxin [5–8], both binding to a common receptor and exerting similar biological effects [9]. Two types of TNF receptors have been characterized biochemically and by reactivity of two sets of monoclonal antibodies (MAb) [10, 11]; the 75-kDa and the 55-kDa TNF receptors are differentially expressed on various cell lines [11, 12]. Antibodies to the 55-kDa molecule have been shown to exert functional TNF-like effects on U937 cells, Fs4 fibroblasts, and endothelial cells inducing cytotoxicity, interleukin-6 production, and proliferation [12]. Recently the cDNAs of the 75-kDa and of the 55-kDa TNF receptors have been cloned [13–16]. Sequence data revealed a 38.5% amino acid identity of the 75-kDa TNF receptor with CD40, a molecule which is expressed on neoplastic and normal B cells and gives a strong cell cycle progression signal in B cells [17]. We studied the expression of the 75-kDa and 55-kDa TNF receptors on normal and malignant human B cells. We show that first the 75-kDa and subsequently the 55-kDa TNF receptor is expressed on the surface of normal activated B cells. B-cell chronic lymphatic leukemia (B-CLL) and hairy cell leukemia (HCL) cells express both types of receptors after in vitro stimulation. A MAb binding to the 75-kDa receptor inhibits proliferation of normal B cells and of HCL cells, indicating that this receptor is functionally involved in the TNF-induced B-lymphocyte proliferation.