Production of Autoantibodies Associated with Polyclonal Activation in Yersinia enterocolitica O:8‐Infected Mice

Abstract

Polyclonal lymphocyte stimulation is one of the immunomodulatory mechanisms induced by arthritogenic pathogens. In this study we examined the polyclonal activation potential of a virulent strain of Y. enterocolitica serotype O:8 (WA 2707+) and its plasmidless isogenic pair (WA 2707−). SPF Swiss mice were infected intragastrically and spleen cells were obtained on days 7, 14, 21, 28, 35 and 42 after infection. The number of cells secreting nonspecific immunoglobulins of IgG, IgM and IgA isotypes was determined by the ELISPOT technique. The presence of serum‐specific antibodies was investigated by ELISA and the presence of autoantibodies by dot‐blot assay. Although the patterns of infection of the two bacterial strains were almost the same, only the animals infected with the virulent strain presented clinical anomalies. Neither arthritic nor inflammatory signs were observed in the joints of the infected animals. The greatest activation observed was that of the nonspecific IgM‐secreting cells, and their peak of secretion occurred between the 28th and the 42nd day after infection, for both strains of Y. enterocolitica O:8. Only the animals infected with the virulent strain (WA 2707+) produced IgG‐specific antibodies in the serum, from the 28th day after infection. The serum of animals infected with either strain showed reactivity to all the autologous constituents tested, mainly on the 28th and 42nd day after infection. It was concluded that infection of mice with either the virulent strain of Y. enterocolitica O:8 or with its plasmidless isogenic pair resulted in the polyclonal activation of the splenic B lymphocytes including some autoreactive clones.

The context of tetanus toxoid application influences the outcome of antigen‐specific and self‐directed humoral immune response

“…Various data that connect exposure to micAg, during infections (1–4) and vaccinations (5–8), to autoAb production have been published in recent years. Among the possible mechanisms that contribute to autoAb generation, the most cited mechanisms are molecular mimicry (9, 10) and polyclonal cell activation (11, 12). Available data show that long‐term stimulation by micAg is accompanied by augmentation of self‐reactivity, but not by obvious induction of autoimmune diseases (13).…”

SARS-CoV-2 infection relaxes peripheral B cell tolerance

“…While the majority of individuals infected with SARS-CoV-2 do not suffer from severe COVID-19 disease (Salzberger et al, 2021), a considerable subset of individuals develop a severe infection that is accompanied by robust proinflammatory cytokine production (Ragab et al, 2020;Yang et al, 2021). Autoantibody production has long been appreciated to be a consequence of inflammatory settings that not only include bacterial (Ramos et al, 2005;Isenberg et al, 1987;Jafarzadeh et al, 2013) and viral infections (Duca et al, 2017;Ruggeri et al, 2008;Kerr and Boyd, 1996;Bartholomaeus et al, 1988;Tanay, 2017) but also tissue injury (Davies et al, 2007;Burbelo et al, 2010). Thus, it is not surprising that autoantibody production in severe SARS-CoV-2 infection has been reported (Bastard et al, 2020;Chang et al, 2021;Wang et al, 2021;Xiao et al, 2020;Su et al, 2022), raising concern that autoantibodies may contribute to disease pathology, as previously reported for viral infections with Hepatitis B (Barzilai et al, 2007), the original SARS-CoV-1 (Lin et al, 2005;Yang et al, 2005), and the Dengue viruses (Lin et al, 2006).…”

Development of Acute Transverse Myelitis following COVID-19 Infection: A Review on the Potential Pathways

“…The polyclonal activators originating from microorganisms are typically parts of the cell membranes, the cytosol, or excretion/secretion products [83]. In numerous animal models of viral, parasitic, and bacterial infection, the presence of a potent polyclonal B-cell response resulting in hyper-ɤ-globulinemia and the release of autoantibodies has been observed [71, 87]. Molecular mimicry and bystander activation have been suggested as the most likely mechanisms underlying SARS-CoV-2-associated ATM [35].…”