Functional expression of the calcitonin receptor by human T and B cells

Abstract

The calcitonin receptor (CTR) is a seven-transmembrane–domain G-protein–coupled receptor that regulates calcium metabolism and bone resorption by osteoclasts. Here we demonstrate that high levels are expressed by normal human T and B lymphocytes from tonsils and peripheral blood in relation to their activation status, as CTR + T cells are prone to produce IFN-γ after TCR stimulation. The receptor is also highly expressed on B cells from chronic lymphocytic leukemia patients, thus suggesting a correlation between its expression, their proliferative extent as well as their memory, antigen-experienced phenotype. Moreover, we found that binding of the receptor with salmon calcitonin induces an increase of intracellular calcium 2+ in peripheral lymphocytes. This effect is involved in several lymphocyte immune functions, as cytosolic calcium 2+ levels regulate both cell proliferation and cytokine production. In our hands, the increase of calcium 2+ levels by CTR binding with sCT induced a dose-dependent cell proliferation. We therefore suppose that expression of this functional receptor may contribute to the modulation of cytoplasmic calcium 2+ levels needed to regulate T and B cell activation and perhaps other immune functions.