Adoptively transferred anti-idiotype pulsed B cells mediate autoimmune myocarditis

Abstract

Syngeneic mice receiving adoptively transferred enriched B cells or splenocytes pulsed in vitro with polyclonal anti-idiotypic antibodies (anti-Ids) against anti-CVB3 virus antibodies developed coxsackievirus B3 antigenbinding and virus-neutralizing antibodies during a 30-day period, in addition to overt expression of autoimmune myocarditis. Adoptive transfer of anti-Id pulsed T cells resulted in delayed appearance and transient expression of antiviral antibodies, and antiviral antibodies were marginal to absent in syngeneic animals receiving anti-Id pulsed macrophage populations. Proliferation analysis of recipient splenocytes indicated lack of proliferative capacity in response to monoclonal or polyclonal anti-Ids and only marginal proliferative capacity in response to coxsackievirus B3 virus antigen(s). In vitro assessment of delayed hypersensitivity in recipient animals demonstrated some specific immunity to anti-Ids in recipients receiving splenocytes or T cells. Anti-Ids expressing mimicry for heart-associated and/or viral antigen(s) interacting with B cells or other accessory cells suggest an autoantibody or anti-Id triggering of B-cell-mediated mechanisms involved in the development of myocarditis.

Type I IFN‐β gene therapy suppresses cardiac CD8+ T‐cell infiltration during autoimmune myocarditis

“…Passive transfer of anticardiac myosin antibodies from MCMV‐infected mice induced inflammation and necrosis of the myocardium in uninfected recipient mice 41 . Similarly, adoptive transfer of B cells or splenocytes pulsed in vitro with anti‐idiotypic antibodies against anti‐CB3 antibodies induced both antibody production and myocarditis in recipient mice 42 . Efficacious IFNB treatment was associated with reduced B‐cell infiltration in the myocardium during the chronic phase.…”

“…Autoantibodies binding to cardiac myosin, which cross‐react with viral antigenic determinants, are implicated in the development of chronic disease 8 , 41 . Previous studies have demonstrated that B cells mediate autoimmune myocarditis 42 . Passive transfer of anticardiac myosin antibodies from MCMV‐infected mice induced inflammation and necrosis of the myocardium in uninfected recipient mice 41 .…”