Role of helper T cells in the loss of B cell anergy mediated by the absence of Tregs (115.6)

Abstract

Regulatory T cells (Tregs) are crucial for the maintenance of immune tolerance and the absence of Tregs results in significant autoantibody production. This suggests that Tregs play a key role in B cell tolerance. The mechanism by which Tregs regulate B cell tolerance has yet to be resolved but has important implications for our understanding of autoimmunity. Using both constitutive and inducible models, we show that the absence of Tregs results in autoantibody production, due to the loss of B cell anergy. Further studies show that this is dependent on the presence of helper T cells. We propose that the absence of Tregs results in the dysregulation of helper T cells that drive the loss of B cell anergy. Interestingly, our studies show the expansion of a CD4+GL7+ population in the absence of Tregs. Subsequent analysis shows that many of these cells express CXCR5 and thus resemble germinal-center TFH cells, an observation confirmed by their expression of Bcl6 and IL-21. We hypothesize that the absence of Tregs drives the expansion of TFH cells that play a role in the loss of B cell anergy. Characterization of this proposed mechanism may unveil new strategies for the treatment or prevention of autoantibody-mediated autoimmune diseases.