The impact of Staphylococcus aureus infection on human B cell responses

Abstract Staphylococcus aureus, S. aureus, is a growing concern in medicine due to the rise of antibiotic resistant strains, such as Methicillin Resistant Staphylococcus aureus (MRSA). Infection and clearance of this bacterium does not lead to immunity to future infections in humans. S. aureus utilizes a variety of virulence factors in order to evade and actively suppress an effective immune response; one of particular importance to humoral immunity is Staphylococcus Protein A (SpA). SpA has the ability to act as a B cell superantigen and anti-opsonin. We address the effects of S. aureus infection on human B cell populations and how the bacterium is able to prevent long lasting, protective immunity; analyzing the effect of infection in humans at the resolution of individual B cells. Focusing on human subjects that have experienced infections, we report on our initial efforts to characterize the kinetics and magnitude of B cell activation by flow cytometry and ELISPOT analysis. Further, we show the ability to derive S. aureus specific monoclonal antibodies (mAbs) from individually sorted B cells in the context of human infection; analyzing the responding B cell BCR repertoire to better understand the human response to this pathogen and how it prevents the generation of useful immunity. It is hoped that specific human monoclonal antibodies to S. aureus virulence factors could be used for therapeutic and prophylactic purposes, or identify epitopes to direct vaccine design.