The diversity of the secondary Salmonella typhimurium-specific B cell repertoire.
This report describes the first analysis of the expressed B cell repertoire specific for a bacterium. In this study, responses to an acetone-killed and dried preparation of Salmonella typhimurium strain TML (AKD-TML) are described. The results show that AKD-TML can stimulate splenic B cells from primed CBA/Ca mice over a wide dose range. The average frequency of secondary TML-specific B cells is 16.4 per 10(5) splenic B cells. This frequency is similar to that observed for another complex, natural antigen, the hemagglutinin of influenza virus. The majority of all secondary TML-specific B cells (greater than 70%) secrete immunoglobulin M, but most of these clones also secrete other isotypes of which immunoglobulins G2 and A are the most prevalent. Analysis of the specificity of secondary TML-specific B cells showed that the vast majority of these B cells were specific for the lipopolysaccharide (LPS) molecule. Moreover, fine specificity analysis demonstrated that approximately two-thirds of these anti-LPS-specific B cell clones are directed against the core polysaccharides or lipid A regions of the LPS molecule, while only about one-third are directed toward the O antigen region. Since anti-S. typhimurium serum antibodies are directed primarily against the O antigens, these studies suggest that the serum levels of antibodies to a given epitope on a bacterial antigen may not be a true reflection of the expressed B cell repertoire when analyzed at the single B cell level. These studies also suggest that the role of antibodies to lipid A molecules in the development of protective immunity to S. typhimurium be reevaluated.
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000145:classification / Q000276:immunology*; D007114:Immunization; D007132:Immunoglobulin Isotypes / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D012486:Salmonella typhimurium / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D007132:Immunoglobulin Isotypes