摘要：SummaryPathogens including autoantigens all failed to induce systemic lupus erythematosus (SLE). We, instead, studied the integrity of host's immune response that recognized pathogen. By stimulating TCR with an antigen repeatedly to levels that surpass host's steady-state response, self-organized criticality, SLE was induced in mice normally not prone to autoimmunity, wherein T follicular helper (Tfh) cells expressing the guanine nucleotide exchange factor DOCK8 on the cell surface were newly generated. DOCK8+Tfh cells passed through TCR re-revision and induced varieties of autoantibody and lupus lesions. They existed in splenic red pulp and peripheral blood of active lupus patients, which subsequently declined after therapy. Autoantibodies and disease were healed by anti-DOCK8 antibody in the mice including SLE-model (NZBxNZW) F1 mice. Thus, DOCK8+Tfh cells generated after repeated TCR stimulation by immunogenic form of pathogen, either exogenous or endogenous, in combination with HLA to levels that surpass system's self-organized criticality, cause SLE.Graphical abstractDisplay OmittedHighlights•Autoimmunity seldom takes place under integrated steady-state immune response•Repeated invasion by pathogen, such as measles virus, is not exceptional but routine in life•DOCK8+Tfh is generated upon TCR overstimulation by pathogen beyond self-organized criticality•Newly generated DOCK8+Tfh induces autoantibodies and SLE, i.e., autoimmunityImmunology; Immune response; Cell biology
