Fcμ receptor as a Costimulatory Molecule for T Cells

Abstract

Fc receptor for IgM (FcμR)-deficient mice display dysregulated function of neutrophils, dendritic cells, and B cells. The relevance of FcμR to human Tcells is still unknown. We show that FcμR is mostly stored inside the cell and that surface expression is tightly regulated. Decreased surface expression on Tcells from elderly individuals is associated with alterations in the methylation pattern of the FCMR gene. Binding and internalization of IgM stimulate transport of FcμR to the cell surface to ensure sustained IgM uptake. Concurrently, IgM accumulates within the cell, and the surface expression of other receptors increases, among them the Tcell receptor (TCR) and costimulatory molecules. This leads to enhanced TCR signaling, proliferation, and cytokine release, in response to low, but not high, doses of antigen. Our findings indicate that FcμR is an important regulator of Tcell function and reveal an additional mode of interaction between B and Tcells.