Interleukin-12 Receptor β2: From Cytokine Receptor to Gatekeeper Gene in Human B-Cell Malignancies

Interleukin (IL)-12 is a cytokine that has been extensively characterized for its immunoregulatory activities. IL-12 binds to a heterodimeric receptor composed of the beta 1 and beta 2 chains. In this review article, we discuss recent findings on the expression and function of IL-12 receptor (IL-12R) in malignant B cells frozen at various stages of differentiation and in their normal counterparts. These studies, together with others performed in ll12rb2 knockout mice, have established the concept that the IL-12R beta 2 gene is a gatekeeper from cancer. We will delineate three paradigms reflecting the differential expression of IL-12R beta 2 in different groups of malignant B cells and discuss the therapeutic perspectives stemming from these studies.