Yersinia Enterocolitica O:3 Isolated from Patients with or without Reactive Arthritis Induces Polyclonal Activation of B Cells and Autoantibody Production In Vivo

Abstract

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.

Echinococcus granulosus glycoconjugates induce peritoneal B cell differentiation into antibody‐secreting cells and cytokine production

“…Polyclonal B cell activation (86,87) and parasite Fc-like receptors (88)(89)(90)(91) are thought to be partially responsible for anti-parasite ineffective humoral responses. In diverse infection models of strong polyclonal B cells responses, the most common isotypic distribution pattern is characterized by an increase in IgG2 subclasses (87,(92)(93)(94). Thus, polyclonal antibodies induction might constitute an evasion strategy exploited by E. granulosus to favour its survival.…”

Erythema nodosum and glatiramer acetate treatment in relapsing-remitting multiple sclerosis

“…Crespo et al [17] showed that lipopolysac- charides (LPS) are linked to anti-myelin, anti-actin or anti-laminin antibodies, and that Yersinia Outermembrane Proteins (Yops) are linked to antimyelin, anti-thyroglobulin or anti -cardiolipin antibodies. Silva et al discovered anti-myelin and anti-myosin antibodies in the sera of Yersinia enterocolitica O:3 infected mice [18]. This polyclonal activation in response to bacterial antigens creates many CICs able to be deposited in subcutaneous tissue and induce EN.…”

Estudo dos mecanismos envolvidos na ativação policlonal dos linfócitos B durante a fase aguda da infecção pelo Plasmodium chabaudi AS.

“…Os ativadores policlonais têm a capacidade de induzir a proliferação de múltiplos clones de linfócitos B, assim como aumentar a expressão de moléculas como classe II do MHC, CD69, CD25 e moléculas costimuladoras como CD80 e CD86 na superfície dos linfócitos B (Nashar et al, 1997;Montes et al, 2002). Os anticorpos produzidos durante a ativação policlonal reconhecem antígenos heterólogos e antígenos homólogos como actina, mioglobulina, miosina, tiroglobulina e DNA (Montes et al, 1996;Hunziker et al, 2003;Silva et al, 2003 (Gobet et al, 1988;Ochsenbein et al, 1999) e, no caso da IgM, participam da resposta imune inata ativando a via clássica do complemento.…”