| Summary: | Staphylococcus aureus is a Gram positive bacterium responsible for significant morbidity and mortality in the developed world. Interestingly, prior infection with this pathogen does not always result in protective immunity; recurrent and chronic infections are common, indicating that humoral immune responses may be disrupted. S. aureus protein A (SpA) is a virulence factor known to be a B cell superantigen; it binds to conserved regions on antibodies expressing the VH3 idiotype. In mouse models SpA causes the expansion and ablation of this B cell population. We hypothesized that SpA may be interfering with the B cell response to S. aureus. We recruited patients experiencing S. aureus infection and analyzed their ongoing humoral immune response to S. aureus by producing monoclonal antibodies (mAbs) from their plasmablast populations. Serologically, these infected patients exhibited responses to known S. aureus virulence factors. Importantly, however, we observed that patients exhibited strong plasmablast responses to SpA, but weak or no responses to other S. aureus virulence factors. S. aureus infection-induced plasmablasts displayed a VH3-skewed response repertoire and evidence of germinal center experience. Additionally, infected individuals' plasmablasts were affinity matured against SpA. We hypothesize that S. aureus is able to evade the host humoral immune response by using SpA to cause a non-specific, immunodominance of germinal center reaction.
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