The normal function of the immune system is to protect the host against infection. The failure of the immune system to recognize its own cells and tissues as ‘self’results in the damage of organs leading to their malfunction and causing auto immune disease. Although each autoimmune disease is unique and leads to the dysfunction of a specific organ or population of cells, there is one common feature between many of them–sex-biased predisposition. It is well known that females are more predisposed to many autoimmune diseases than males although the reason for this sex bias is not completely understood. A significant body of research suggests roles for sex hormones as well as genetic factors in the development and/or progression of autoimmunity [1–3]. Although hormones and genetics are known to contribute to the incidence of autoimmunity, little is known about how these phenomena actually affect the immune system to subvert it from its normal function. In this article, we will briefly describe the main factors that are important for sex bias in autoimmune diseases and will review recent findings on a new population of B cells that predominantly appears in females and plays a role in autoimmunity [4, 5].