Glutamate signaling through the kainate receptor is critical for human B cell IgE production (91.9)

Abstract

Abstract Glutamate, the major excitatory neurotransmitter, has recently been implicated in a variety of diseases. Patients with HIV, certain cancers, and autoimmune illnesses have elevated levels of glutamate in the periphery. While glutamate receptor signaling has been examined in T cells, there are currently no published observations on the effects of glutamatergic stimuli on B cells. Human B cells were first examined for the presence of glutamate receptors via RT-PCR and Western Blot. The kainate receptor (KAR), a specific subtype of ionotropic glutamate receptor was found on human B cells. We found that KAR activation increased ADAM10 mRNA which is in agreement with receptor activity in the CNS. A significant corresponding increase in CD23 released into the supernatant was seen as ADAM10 has been identified as the protease responsible for CD23’s ectodomain shedding. Remarkably, we also detect a strong increase in cellular proliferation and IgE synthesis. Thus, we report for the first time the unique presence of a neurotransmitter receptor and that activation of this receptor could serve as a novel mechanism for enhancing B cell activation. This enhancement has implications for allergic and autoimmune diseases.