A B cell superantigen-induced persistent "Hole" in the B-1 repertoire.
The bacterial toxin protein A from Staphylococcus aureus (SpA) interacts with B cell antigen receptors encoded by variable region heavy chain (V(H)) clan III genes via a V region framework surface that has been highly conserved during the evolution of the adaptive immune system. We have investigated the consequences of exposure to this prototypic B cell superantigen, and found that treatment of neonates or adults induces a T cell-independent deletion of a large supraclonal set of susceptible B cells that includes clan III/V(H) S107 family-expressing lymphocytes. In studies of different SpA forms, the magnitude of the induced deletion directly correlated with the V(H)-specific binding affinity/avidity. Upon cessation of SpA exposure, the representation of conventional splenic (B-2 subset) lymphocytes normalized; however, we found that the V(H) family-restricted deficit of peritoneal B-1 cells persisted. SpA treatment also induced a persistent loss of splenic S107-mu transcripts, with a loss of certain natural antibodies and specific tolerance to phosphorylcholine immunogens that normally recruit protective antimicrobial responses dominated by the S107-expressing B-1 clone, T15. These studies illustrate how a B cell superantigen can exploit a primordial Achilles heel in the immune system, for which B-1 cells, an important source of natural antibodies and host immune responses, have special susceptibility.
Silverman
G J
GJ
Department of Medicine, University of California at San Diego, La Jolla, California 92093-0663, USA. gsilverman@ucsd.edu
Cary
S P
SP
Dwyer
D C
DC
Luo
L
L
Wagenknecht
R
R
Curtiss
V E
VE
D000328:Adult; D000818:Animals; D000915:Antibody Affinity; D001402:B-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007231:Infant, Newborn; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*; D013205:Staphylococcal Protein A / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell; D013205:Staphylococcal Protein A; D018089:Superantigens