Altered expression of the Salmonella typhimurium-specific B-cell repertoire in mice chronically treated with antibodies to immunoglobulin D.
Using a modification of the splenic focus assay, we analyzed the Salmonella typhimurium-specific B-cell repertoire in salmonella-susceptible BALB/c mice. Although these mice normally succumbed to salmonella infection before antibody was produced, they appeared to have splenic S. typhimurium-specific B-cell precursors that could be activated to differentiate and secrete antibody in a manner which was quantitatively and qualitatively identical to that of salmonella-resistant mouse strains. We also analyzed the primary S. typhimurium-specific B-cell repertoire in BALB/c mice that had been chronically treated with antibodies to immunoglobulin D (IgD) and therefore had no surface IgD-positive B cells. Although the frequency of S. typhimurium-specific precursors in these mice was similar to that of control mice, there was an apparent alteration in the isotype distribution pattern in anti-IgD-treated mice. Control mice generated a significantly greater proportion of IgG-secreting clones than did anti-IgD-treated mice. In addition, a greater proportion of S. typhimurium-specific clones from control mice secreted IgG2 than secreted IgG1, and those clones that secreted IgG2 but not IgM, IgG3, or IgG1 were greater than 20-fold more common in control than in anti-IgD-treated mice. Finally, we analyzed the immune response of control and anti-IgD-treated mice to a live avirulent vaccine, S. typhimurium SL3235. Although both groups were protected after challenge with a live virulent S. typhimurium strain, only the control mice made serum antibodies to this vaccine. Taken together, these results show that (i) salmonella-susceptible BALB/c mice have S. typhimurium-specific B cells, (ii) the S. typhimurium-specific B cells in anti-IgD-treated mice may have a restricted capacity to switch heavy-chain classes, (iii) the similarity observed in the frequency of the S. typhimurium-specific precursors for these two groups of BALB/c mice is not reflected in the serum, and (iv) the failure of anti-IgD-treated mice to generate a serum antibody response to SL3235 in the face of complete protection suggests that this model may be used to study cell-mediated immune mechanisms in the apparent absence of humoral immunity.
Fultz
M J
MJ
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
Finkelman
F D
FD
Metcalf
E S
ES
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage*; D000907:Antibodies, Bacterial / Q000032:analysis*; D001402:B-Lymphocytes / Q000145:classification / Q000276:immunology / Q000382:microbiology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D007106:Immune Sera / Q000032:analysis; D007115:Immunization Schedule; D007072:Immunoglobulin D / Q000008:administration & dosage / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000145:classification; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology*; D013154:Spleen / Q000382:microbiology
D000888:Antibodies, Anti-Idiotypic; D000907:Antibodies, Bacterial; D000939:Epitopes; D007106:Immune Sera; D007072:Immunoglobulin D; D007132:Immunoglobulin Isotypes; D011947:Receptors, Antigen, B-Cell; C039951:anti-IgD