Figure 2.

A model to explain how a nonself molecule such as the DNA-binding polyomavirus T antigen, when physically linked to histones through complex formation with nucleosomes, may initiate processes that result in induction of antibodies to DNA. Expressed T antigen forms complexes with nucleosomes.56,68 DNA-specific B cells binding and processing such complexes may simultaneously present peptides derived from T antigen and histones. T cells not tolerant for T antigen will respond, produce IL-2, and proliferate. IL-2 has the potential to induce proliferation of anergic cells and terminate the state of anergy.74,75 During this process, anergic histone-specific T cells receive two different stimuli, the first as a nonspecific, bystander stimulus by IL-2 produced by T-antigen-specific responder T cells and the other by a conventional, antigen-specific stimulus by presented histone peptides. In this situation, T-cell anergy for histones may be terminated. Thus, if DNA-specific B cells present both T antigen and histones to responder T cells, activation of autoimmune, histone-specific T cells and production of anti-DNA antibodies will be the final result. If this process is sustained, affinity maturation of the anti-DNA antibodies may transform them into high-affinity anti-dsDNA antibodies as a consequence of somatic mutations, particularly within the variable CDR regions of the heavy chain65,67,97 (modified from Andreassen et al54). T cells marked in red indicate they are activated.