In Praise of Descriptive Science: A Breath of Fresh AIRE

Abstract

Meyer et al. find that subjects lacking the AIRE gene, critical for self-tolerance in T lymphocytes, show a broad range of autoantibody specificities, which can have extremely high affinities. The data also suggest that some of these autoantibodies can, surprisingly, prevent some types of autoimmunity, particularly type I diabetes.

Figure 1. A Simplified View of T-B Lymphocyte Interactions in the Presence or Absence of the AIRE Gene’s Influence on T Cell Tolerance

Normally, follicular helper CD4⁺ T cells emerge from the thymus with those expressing self-specific T cell receptors either purged or suppressed (upper part of the figure). They are then able to stimulate B cells specific for the same antigen to mutate their antibody genes to achieve higher affinities after a bolus of immunizing antigen or an infection. In AIRE-deficient subjects, it is suggested that the absence of T cell tolerance allows multiple T-B interactions of this sort due to the continuous presence of self-antigen, resulting in the very high affinities seen in Meyer et al. (2016). Here, arrows denote increases in antibody affinity.