Generation of a complement-independent bactericidal IgM against a relapsing fever Borrelia.
The spirochetemia of relapsing fever in mice is cleared by a complement-independent, polyclonal IgM response with reactivity to two prominent Ags of 20 and 35 kDa. In this study, we have dissected the polyclonal IgM Ab response against a relapsing fever spirochete to determine the specificity of its complement-independent bactericidal properties. Our experimental approach selectively generated an IgM murine mAb from the early specific immune response to a variable outer membrane protein. This IgM is bactericidal in the absence of complement and is part of the polyclonal Ab response that mediates the clearance of this bacterium from the blood. Purified monoclonal IgM caused direct structural damage to the outer membrane of the spirochete, in the absence of complement, and protected both B cell- and C5-deficient mice from challenge when administered passively. The direct, complement-independent, bactericidal activity of Abs is a critical mechanism of host defense against infection.
Connolly
Sean E
SE
Department of Molecular Genetics and Microbiology, Center for Infectious Diseases, Stony Brook University, Stony Brook, NY 11794, USA.
Thanassi
David G
DG
Benach
Jorge L
JL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000096:biosynthesis / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000473:pathology; D016470:Bacteremia / Q000276:immunology / Q000382:microbiology / Q000628:therapy; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology / Q000648:ultrastructure; D001770:Blood Bactericidal Activity / Q000276:immunology*; D001898:Borrelia / Q000254:growth & development* / Q000276:immunology* / Q000648:ultrastructure; D015922:Complement C1q / Q000502:physiology; D003182:Complement C5 / Q000172:deficiency; D003165:Complement System Proteins / Q000502:physiology*; D007116:Immunization, Passive / Q000379:methods; D007075:Immunoglobulin M / Q000008:administration & dosage / Q000096:biosynthesis* / Q000097:blood; D008074:Lipoproteins / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012061:Relapsing Fever / Q000276:immunology* / Q000382:microbiology* / Q000517:prevention & control
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D003182:Complement C5; D007075:Immunoglobulin M; D008074:Lipoproteins; D015922:Complement C1q; D003165:Complement System Proteins