Production of autoantibodies associated with polyclonal activation in Yersinia enterocolitica O: 8-infected mice.

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.

Yersinia enterocolitica O:3 isolated from patients with or without reactive arthritis induces polyclonal activation of B cells and autoantibody production in vivo.

The mechanisms by which arthritis-provoking pathogens such as Yersinia enterocolitica interact with the human immune system to produce inflammatory synovitis are not well known. One of the immunomodulating mechanisms used against these pathogens is the polyclonal activation of lymphocytes. In this study, we investigated the extent of the B-lymphocyte activation induced in mice by a strain of Y. enterocolitica O:3 (FCF 526) isolated from a patient with arthritis, and compared it with two other strains, a virulent one (FCF 397[+]) isolated from a patient without arthritis and its plasmidless isogenic pair (FCF397[-]). Also we investigated the production of autoantibodies in mice infected with these different strains. SPF Swiss mice were infected intravenously with a suspension of Y. enterocolitica. Spleen cells were taken on days 7, 14, 21 and 28 after infection and the number of cells secreting nonspecific and specific antibodies of IgG1, IgG2a, IgG2b, IgG3, IgM and IgA isotypes were determined by the ELISPOT technique. The presence of autoantibodies in mouse serum was investigated by the dot-blot assay. The pattern of infection of the three bacterial strains were almost the same. We observed a general increase in the number of nonspecific Ig-secreting cells with all three strains, and the greatest increases observed were in the IgG2a and IgG3 isotypes. Only a small fraction of the immunoglobulins detected were antibacterial, suggesting that the rest resulted from polyclonal B cell activation. The strain isolated from the patient with arthritis (FCF526) induced the greatest production of autoantibodies, coinciding with the period in which the greatest activation of nonspecific B lymphocytes was seen. There were no signs of arthritis or inflammation in the joints of the infected animals. Based on our results, we were unable to determine whether there is an association between the arthritogenic capability of Y. enterocolitica and polyclonal activation of B cells.

Ativaçäo de linfócitos B das placas de Peyer de camundongos infectados por via gástrica com Yersinia enterocolitica O: 8 / Peyer's patches B lymphocyte activation of mice infected by gastric route with Yersinia enterocolitica O: 8

Foi realizada infecçäo experimental de camundongos Swiss, "SPF", com amostra virulenta de Y. enterocolitica O: 8, inoculada por via gástrica, com o objetivo de verificar a ativaçäo de células B presentes nas placas de Peyer dos animais e comparar com aquela provocada por uma amostra isogênica, curada do plasmídeo de virulência. Para tanto, foi determinada a cinética de células secretoras de imunoglobulinas inespecíficas e específicas dos diferentes isótipos (IgG, IgA e IgM), pela técnica de ELISPOT e pesquisada a presença de anticorpos específicos anti-Yersinia nos soros dos animais infectados, por meio de ELISA. Foi verificada uma ativaçäo das células secretoras de imunoglobulinas inespecíficas nas placas de Peyer. Para a amostra virulenta, a maior ativaçäo ocorreu no número de células secretoras de IgG, e o pico de secreçäo ocorreu no 35§ dia pós-infecçäo (aumento de 8,9 vezes em relaçäo aos animais controles). Nos animais infectados com a amostra avirulenta, a maior ativaçäo ocorreu para o isótipo IgA, no 21§ dia pós-infecçäo (aumento de 16,1 vezes). Näo foi possível a detecçäo de células secretoras de Igs específicas. Anticorpos específicos do isotipo IgG foram detectados apenas nos soros dos animais infectados com a amostra virulenta, a partir do 28§ dia pós-infecçäo. Conclui-se que ambas as amostras de Y. enterocolitica O: 8 provocaram ativaçäo policlonal de linfócitos B das placas de Peyer.