Critical role for IgM in host protection in experimental filarial infection.
We have previously shown that B cells (in particular B1 cells) are important in host protection against brugian infections in a murine i.p. model. In this study, we show that mice deficient in circulating IgM (secIgM-/-), but otherwise normal in their humoral responses, manifest a significant impairment in worm elimination, suggesting that one critical B cell function is the production of Ag-specific IgM. Efficient elimination of larvae is IgM dependent for both primary and challenge infections. The ability to eliminate worms is restored in secIgM-/- mice by administering sera from primed mice. We corroborated these in vivo studies with in vitro observations which show that IgM is the only isotype that reacts strongly with the surface of Brugia L3. Furthermore, activated peritoneal exudate cells adhere to L3 only in the presence of filaria-specific sera or IgM purified from them. This attachment is not reduced by heat inactivation of the serum, suggesting complement independent activity. Peritoneal exudate cells from primed mice, especially activated macrophages, carry high levels of IgM on their surfaces. Our observations suggest that an IgM-mediated reaction initiates the formation of host-protective granulomas.
Rajan
Bhargavi
B
Department of Pathology, University of Connecticut Health Center, Farmington, CT 06032, USA. rajan@neuron.uchc.edu
Ramalingam
Thirumalai
T
Rajan
Thiruchandurai V
TV
D000818:Animals; D001666:Binding Sites, Antibody; D017179:Brugia pahangi / Q000254:growth & development / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D005368:Filariasis / Q000235:genetics / Q000276:immunology* / Q000469:parasitology / Q000628:therapy; D007106:Immune Sera / Q000378:metabolism; D007116:Immunization, Passive; D007132:Immunoglobulin Isotypes / Q000235:genetics / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use; D007075:Immunoglobulin M / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D007106:Immune Sera; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; C033027:secretory IgM