Role of inhibitory signaling in peripheral B cell tolerance.

At least 20% of B cells in the periphery expresses an antigen receptor with a degree of self-reactivity. If activated, these autoreactive B cells pose a risk as they can contribute to the development of autoimmune diseases. To prevent their activation, both B cell-intrinsic and extrinsic tolerance mechanisms are in place in healthy individuals. In this review article, I will focus on B cell-intrinsic mechanisms that prevent the activation of autoreactive B cells in the periphery. I will discuss how inhibitory signaling circuits are established in autoreactive B cells, focusing on the Lyn-SHIP-1-SHP-1 axis, how they contribute to peripheral immune tolerance, and how disruptions of these circuits can contribute to the development of autoimmunity.