Anthrax Lethal Toxin Has Direct and Potent Inhibitory Effects on B Cell Proliferation and Immunoglobulin Production

摘要: Protective host immune responses to anthrax infection in humans and animal models are characterized by the development of neutralizing Abs against receptor-binding protective Ag (PA), which, together with lethal factor (LF) protease, composes toxin (LT). We now report that B cells, turn, targets for LT. Anthrax PA directly binds primary resulting LF-dependent cleavage MAPK kinases (MAPKKs) disrupted signaling downstream targets. Although not LT treatment causes severe cell dysfunction, greatly reducing proliferative IL-4-, anti-IgM-, and/or anti-CD40 stimulation. Moreover, cells treated vitro or isolated from mice vivo have a markedly diminished capacity proliferate produce IgM response TLR-2 TLR-4 ligands. The suppressive effects on function occur at picomolar concentrations sublethal doses vivo. These results indicate inhibits vivo, revealing potential mechanism through which pathogen could bypass responses.