Reductions in C4 levels may predispose individuals to @entity281 with encapsulated bacteria as well as @entity792 . In this study, we examined the role C4 has in protection against @entity328 -induced @entity792 . Mild @entity1729 with serotype 19F pneumococci selectively induced systemic anti-dsDNA IgA production in naive C4(-/-) @entity19 , but not in C3(-/-) or wild-type @entity19 . Systemic challenge with virulent serotype 3 pneumococci also induced anti-dsDNA IgA production in immune C4(-/-) @entity19 . Remarkably, @entity16290 ( @entity16290 ) vaccination alone induced C4(-/-) @entity19 to produce increased anti-dsDNA IgA levels that were maintained in some @entity19 for months. These effects were most pronounced in female C4(-/-) @entity19 . Importantly, immunization-induced increases in anti-dsDNA IgA levels were strongly associated with increased IgA deposition in kidneys. Cross-reactivity between pneumococcal Ags and dsDNA played a partial role in the induction of anti-dsDNA IgA, but a major role for @entity16290 -associated @entity8932 agonists was also revealed. Administration of the @entity26789 antagonist, OxPAPC, at the time of @entity16290 immunization completely blocked the production of anti-dsDNA IgA in C4(-/-) @entity19 without suppressing @entity16290 -specific Ab production. The @entity8932 agonist, Pam3CSK4, similarly induced anti-dsDNA IgA production in C4(-/-) @entity19 , which OxPAPC also prevented. @entity558 , a @entity1990 agonist, had no effect. Pam3CSK4, but not @entity558 , also induced dsDNA-specific IgA production by C4(-/-) splenic IgA(+) B cells in vitro, indicating that @entity8932 agonists can stimulate autoantibody production via B cell-intrinsic mechanisms. Collectively, our results show an important role for C4 in suppressing autoantibody production elicited by cross-reactive Ags and @entity8932 agonists associated with @entity2260 .

C4 Deficiency Is a Predisposing Factor for XXXX -Induced Autoantibody Production.

@entity558 :: ('MESH:C536528', 'Disease') :: ['LPS'] @entity26789 :: ('24088;21898', 'Gene') :: ['TLR2/4'] @entity16290 :: ('MESH:C564877', 'Disease') :: ['PPS', 'pneumococcal polysaccharide'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity2260 :: ('2104', 'Species') :: ['S. pneumoniae'] @entity281 :: ('MESH:D007239', 'Disease') :: ['infection'] @entity792 :: ('MESH:D001327', 'Disease') :: ['autoimmunity'] @entity1729 :: ('MESH:D012141', 'Disease') :: ['respiratory infection'] @entity8932 :: ('24088(Tax:10090)', 'Gene') :: ['TLR2'] @entity1990 :: ('21898(Tax:10090)', 'Gene') :: ['TLR4'] @entity328 :: ('1313', 'Species') :: ['Streptococcus pneumoniae']
@entity328 :: (1313,Species) :: ['Streptococcus pneumoniae']
