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 gents 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 supra-clonal set of susceptible B cells that includes dan III/V-H S107 family-expressing lymphocytes. III studies of different SpA forms, the magnitude of the induced deletion directly cell-elated 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, 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 super-antigen call exploit a primordial Achilles heel in the immune system, for which B-l cells, an important source of natural antibodies and host immune responses, have special susceptibility.