Molecular Characterization of Virus-induced Autoantibody Responses

Abstract

Here we present a comprehensive molecular mapping of virus-induced autoimmune B cell responses obtained by serological identification of antigens by recombinant expression cloning analysis. Immunoscreening of cDNA expression libraries of various organs (lung, liver, and spleen) using sera from mice infected with cytopathic (vaccinia virus [VV]) or noncytopathic (lymphocytic choriomeningitis virus [LCMV]) viruses revealed a broad specificity of the elicited autoantibody response. Interestingly, the majority of the identified autoantigens have been previously described as autoantigens in humans. We found that induction of virus-induced autoantibodies of the immunoglobulin G class largely depends on the CD40–CD40L-mediated interaction between T and B cells. Furthermore, antibody titers against a number of autoantigens were comparable to the concomitantly induced antiviral antibody response. Comparison of serum reactivity against a selected panel of autoantigens after infection with VV, LCMV, or vesicular stomatitis virus showed that the different virus infections triggered distinct autoantibody responses, suggesting that virus infections may leave specific “autoantibody fingerprints” in the infected host.

The Tumor Antigen Cyclin B1 Hosts Multiple CD4 T Cell Epitopes Differently Recognized by Pre-Existing Naive and Memory Cells in Both Healthy and Cancer Donors

“…7 (30, 31). As mentioned by Vella et al (30), the tumor Ag MUC-1 could also be the target of Abs in noncancer patients that could have been elicited by infection (56), as formally observed for GM-CSF autoantibodies (57). We cannot completely exclude a link between the anti-CCNB1 humoral response and the memory CCNB1-specific CD4 T cells that we detected in the short-term T cell assays, but there was no correlation between T and B cell responses.…”

Healthy individuals have T-cell and antibody responses to the tumor antigen cyclin B1 that when elicited in mice protect from cancer

“…We have published that several nonneoplastic events known to affect MUC1-expressing tissues, such as mumps virus infection of MUC1ϩ salivary glands or mastitis affecting MUC1ϩ breast ducts, correlate with the presence of anti-MUC1 antibody in healthy individuals (40). Compelling evidence for a nonneoplastic event eliciting immune responses to self antigens was obtained recently by studying mice recovering from viral infections (41). Mice infected with either vaccinia virus or lymphocytic choriomeningitis virus generated antibodies against the viral antigens against many host cell proteins involved in cell cycle progression and cell adhesion, some of which had been characterized as human tumor-associated antigens.…”

Evolving concepts of specificity in immune reactions

“…Like some mAbs from HIV-1-infected individuals, serum Abs that bind cardiolipin and other self-Ags have long been known to occur in some persistent infections in humans (e.g., Epstein-Barr virus, hepatitis B virus, syphilis treponeme) and in mice (e.g., vaccinia virus) (56). Indeed, myeloma proteins, where evidence for Ab multireactivity surfaced about 40 y ago, have recently been found to have multiple V region mutations, and the myeloma tumor cells that produce them have been found to arise from postgerminal center memory B cells (57,58).…”