Journal
MICROBES AND INFECTION
Volume 7, Issue 15, Pages 1501-1511Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.micinf.2005.05.008
Keywords
Staphylococcus aureus; infection; staphylococcal protein A; superantigens; B lymphocytes; antibody formation
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Funding
- NIAID NIH HHS [AI40305, AI46637] Funding Source: Medline
- NIAMS NIH HHS [AR47360] Funding Source: Medline
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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 Fc gamma, 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 VHIII-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 VHIII-encoded antibodies specific for SpA devoid of Fc gamma-binding ability (MSpA) than an isogeneic spa deletion mutant strain. The VHIII-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. (C) 2005 Elsevier SAS. All rights reserved.
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