A complex interplay of cells, soluble macromolecules, and antigen lead
to a productive immune response that evolved for the survival of spec
ies. While the immune system is intended to protect from foreign agent
s, such as bacterial and viral infection, the presence of autoimmune d
iseases indicates that the system is not perfect in differentiating an
tigen that may cause harm from benign self constituents. The concept o
f epitope spreading, where many determinants on an offending antigen a
re the focus of immune attack, is an efficient means of clearing an in
fectious agent. However, the same mechanisms that lead to a diverse im
mune response may be harmful when the targets of attack are self tissu
es or self macromolecules. This review will examine the forms of self
antigens that may initiate autoimmunity and the potential role of B ly
mphocytes, as autoantigen-presenting cells, as one mechanism by which
diversification of autoimmunity may occur.