Commentary: Fc Gamma Receptors are Expressed in the Developing Rat Brain and Activate Downstream Signaling Molecules upon Cross-Linking with Immune Complex.

Abstract

During the past 20 years, a number of studies have reported IgG antibodies against viral or self-antigens in the developing human brain. Although the mechanisms by which they gain access to the developing brain are not yet clear, a subset of these antibodies has been linked to increased risk for neurodevelopmental disorders1–11. At first glance, such effects are expected to be mediated by IgG binding to its cognate Fcγ receptors (FcγR) on resident immune cells (such as microglia) in the brain and subsequent activation of local innate immune responses. However, considering that antibodies linked to neurodevelopmental disorders have subsequently been shown to recognize intracellular antigens expressed in neurons and astrocytes7, it is tempting to hypothesize that these autoantibodies could derail normal neurodevelopment by binding to their target antigens expressed on non-immune cells in the brain. Neuronal uptake of IgG antibodies against intracellular neuronal antigens has previously been shown and, in some cases, is thought to be mediated via clathrin-dependent endocytosis of IgG bound to FcγR in these neurons12, 13. In combination with recent studies showing functional expression of FcγRI in adult rat dorsal root ganglion neurons14–16, these findings prompted us to conduct the first comprehensive investigation of FcγR expression and signaling on neurons and astrocytes in the developing rat brain. In our study, we documented sex-independent in vivo expression.