Researchers Identify Quality Control Regulatory Cells That Prevent the Production of Autoantibodies
The discovery of an immune cell quality control mission may have put scientists a step closer to understanding how autoimmune conditions such as multiple sclerosis arise.
University of Alabama at Birmingham researchers identified regulatory immune cells with the quality control mission of destroying antibody-producing B-cells that mistakenly target the body’s own tissue after an infection. An autoimmune disease is one in which the immune system attacks healthy tissue or organs instead of invaders.
Eventually, the insight could lead researchers to new approaches for treating MS and other conditions caused by aberrant immune reactions.
The Alabama researchers were studying the processes involved in the body’s defense against a real threat — the influenza virus — when they discovered a population of immune cells whose action is relevant to autoimmune diseases.
“This research gives us clues of what to look for when we look at how autoimmune disease develops,” André Ballesteros-Tato, who led the research, said in a press release. He is an assistant professor in the university’s Department of Medicine.
The study noted that T follicular regulatory (TFR) cells appeared in the late stages of influenza infection. Their objective was to prevent the immune system from generating self-reactive antibodies — that is, those that attack the body’s own tissue.
These cells are poorly understood, the researchers explained. Their experiments, published in the journal Nature Immunology, focused on the molecular events surrounding the cells’ actions. The title of their article was “Dynamic regulation of T follicular regulatory cell responses by interleukin 2 during influenza infection.”
The team discovered that about a week after the infection, levels of an immune regulator called the IL-2 protein increased. This triggered the multiplication of common regulatory T-cells, or Tregs. When this phase of the immune reaction was fading, TFR cells started multiplying, reaching peak numbers about a month after infection.
The formation of the TFR cells was therefore tightly linked to the processes controlling Treg production, researchers said, with falling levels of IL-2 allowing the new phase of the immune response.
The TFR cells migrated to the lymph nodes — the headquarters of antibody-producing B-cells. Here, B-cells proliferate and change their antibody-producing genes to create new, stronger antibodies. But sometimes the gene changes, or mutations, give rise to an antibody that attacks the body, instead of invaders.
Researchers discovered that TFR cells prevented B-cells, which gave rise to autoantibodies, from accumulating in the lymph nodes. Importantly, the TFR cells had no impact on the immune processes targeting the influenza virus.
When researchers prevented TFR cells from forming or removed them from mice, the animals started producing autoantibodies, they explained.
While this suggested that people with autoimmune diseases may have flawed TFR processes, the study did not investigate this, making the topic a possibility for future studies.