How the body limits the amount of circulating IgA antibody in the blood on mice, and thereby lowering the risk of kidney disease is described in a paper published online this week in Nature Immunology. The findings could help with therapeutic intervention for those afflicted with IgA-mediated autoimmunity.
Shao-Cong Sun and colleagues studied B immune cells, which are the body’s antibody-producing cells. Activation of these B cells ramps up antibody production and can induce a process known as immunoglobulin class switching, a genetic process that dictates the type of antibody that is eventually produced. Sun’s study shows a regulatory molecule called TBK1 specifically prevents class switching to IgA. Mice that lacked TBK1 expression in B cells produced higher amounts of IgA in their serum, including autoantibodies that recognize self-tissues. These mice developed renal dysfunction as autoimmune IgA complexes accumulated in their kidneys, mimicking IgA-related human pathologies.