Association between polyclonal B cell activation and the presence of autoantibodies in mice infected with Yersinia enterocolitica O:3

Abstract

Eight-week old conventional female Swiss mice were inoculated intravenously with Yersinia enterocolitica O:3. A second group of normal mice was used as control. Five mice from each group were bled by heart puncture and their spleens were removed for spleen cell collection on the 3rd, 5th, 7th, 10th, 14th and 21st day after infection. Immunoglobulin-secreting spleen cells were detected by the isotypespecific protein A plaque assay. Total immunoglobulin levels were determined in mouse serum by single radial immunodiffusion and the presence of autoantibodies was determined by ELISA. We observed a marked increase in the total number of cells secreting immunoglobulins of all isotypes as early as on the 3rd day post-infection and the peak of secretion occurred on the 7th day. At the peak of the immunoglobulin response, the total number of secreting cells was 19 times higher than that of control mice and most immunoglobulin-secreting cells were of the IgG 2a isotype. On the 10th day post-infection, total serum immunoglobulin values were 2 times higher in infected animals when compared to the control group, and continued at this level up to the 21st day post-infection. Serum absorption with viable Y. enterocolitica cells had little effect on antibody levels detected by single radial immunodiffusion. Analysis of serum autoantibody levels revealed that Y. enterocolitica infection induced an increase of antimyosin and anti-myelin immunoglobulins. The sera did not react with collagen. The present study demonstrates that Y. enterocolitica O:3 infection induces polyclonal activation of murine B cells which is correlated with the activation of some autoreactive lymphocyte clones.

Effects of Yersinia enterocolitica O:3 Derivatives on B Lymphocyte Activation In Vivo

“…The production of autoantibodies may result from polyclonal B lymphocyte activation. We have shown that this association does occur in mice infected with Y. enterocolitica O:3 (22).…”

“…We have previously demonstrated that conventional Swiss mice infected with the same strain of Y. entero- colitica developed polyclonal activation of B lymphocytes. This activation was not limited to certain isotypes of immunoglobulins since the number of secretory cells of all isotypes was increased, but IgG 2a -secreting cells did increase more strongly, compared to controls (23).…”

“…Regarding the pathogenesis of reactive arthritis, one hypothesis is that the autoimmune response seen in some patients with yersiniosis is the result of the polyclonal activation of B lymphocytes and concomitant autoantibody development. In fact, polyclonal activation of B lymphocytes in conventional Swiss mice infected by Y. enterocolitica O:3 strain was first demonstrated in our laboratory (23). On the one hand, it has been postulated that LPS may be one factor responsible for reactive arthritis (8); on the other, the role of Yersinia outer membrane proteins (Yops) in the pathogenesis of reactive arthritis has not been fully elucidated yet (21).…”

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

“…Polyclonal activation of B lymphocytes in Swiss mice infected with a low-pathogenicity strain, Y. enterocolitica O:3, was first demonstrated in our laboratory (29). Furthermore, Crespo et al (7) demonstrated that Y. enterocolitica O:3 derivatives, such as LPS and Yops, induce polyclonal activation of B lymphocytes.…”