Summary: A complex interplay of cells, soluble macromolecules, and antigen lead to a productive immune response that evolved for the survival of species. While the immune system is intended to protect from foreign agents, such as bacterial and viral infection, the presence of autoimmune diseases indicates that the system is not perfect in differentiating antigen that they cause harm from benign self constituents. The concept of epitope spreading, where many determinants on an offending antigen are the focus of immune attack, is an efficient means of clearing an infections agent. However, the same mechanisms that lead to a diverse immune response may be harmful when the targets of attack are self tissues or self macromolecules. This review with examine the forms of self antigens that may initiate autoimmunity and the potential role of B lymphocytes, as autoantigen-presenting cells, as one mechanism by which diversification of autoimmunity may occur.