Bacterial cell wall-expressed protein A triggers supraclonal B-cell responses upon in vivo infection with Staphylococcus aureus

• We have previously shown that staphylococcal protein A (SpA) anchored to the cell wall of Staphylococcus aureus acts as a virulence factor in septic arthritis. Apart from the ability of SpA to interact with Fcgamma, it also binds to Fab-regions with immunoglobulin heavy chains encoded by the V(H) clan III gene family. The objective of the present study was to investigate whether in vivo expression of SpA by staphylococci induces V(H)III-dependent supraclonal B-cell responses, and whether such responses may affect the ability of the host to produce anti-staphylococcal antibodies. Upon primary infection of mice, a SpA-expressing staphylococcal strain gave rise to significantly higher serum levels of V(H)III-encoded antibodies specific for SpA devoid of Fcgamma-binding ability (MSpA) than an isogeneic spa deletion mutant strain. The V(H)III-dependence of MSpA-specific antibody responses was affected by the size of the staphylococcal inoculum, and differed for IgM and IgG isotypes. Mice that had recovered from a prior mild infection from a SpA-expressing strain were protected against infection-induced weight loss upon reinfection. Although no lasting MSpA-specific IgG was induced by previous mild infection, these protected mice possessed IgG specific for clumping factor A, a conventional staphylococcal protein antigen. Our findings demonstrate that the expression of a B-cell superantigen during staphylococcal infection causes supraclonal changes to the immune system. Notably, while superantigen-triggered B-cell responses do not favor the development of SpA-specific memory B-cells, such responses do not interfere with the development of antibodies specific for a staphylococcal protein antigen associated with protective immunity.

Nyckelord

Animals

Antibodies

Bacterial/blood

B-Lymphocytes/*immunology

Body Weight

Cell Wall/chemistry/*immunology

Coagulase/immunology

Disease Models

Animal

Enzyme-Linked Immunosorbent Assay

Female

Immunoglobulin G/blood

Immunoglobulin M/blood

Mice

Staphylococcal Infections/*immunology

Staphylococcal Protein A/*immunology

Staphylococcus aureus/*immunology

Superantigens/*immunology

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