B1 B lymphocytes play a critical role in host protection against lymphatic filarial parasites.
Host defense against multicellular, extracellular pathogens such as nematode parasites is believed to be mediated largely, if not exclusively, by T lymphocytes. During our investigations into the course of Brugia malayi and Brugia pahangi infections in immunodeficient mouse models, we found that mice lacking B lymphocytes were permissive for Brugian infections, whereas immunocompetent mice were uniformly resistant. Mice bearing the Btk(xid) mutation were as permissive as those lacking all B cells, suggesting that the B1 subset may be responsible for host protection. Reconstitution of immunodeficient recombination activating gene (Rag)-1(-/)- mice with B1 B cells conferred resistance, even in the absence of conventional B2 lymphocytes and most T cells. These results suggest that B1 B cells are necessary to mediate host resistance to Brugian infection. Our data are consistent with a model wherein early resistance to B. malayi is mediated by humoral immune response, with a significant attrition of the incoming infectious larval load. Sterile clearance of the remaining parasite burden appears to require cell-mediated immunity. These data raise the possibility that the identification of molecule(s) recognized by humoral immune mechanisms might help generate prophylactic vaccines.
Paciorkowski
N
N
University of Connecticut Health Center, Farmington, Connecticut 06030-3105, USA.
Porte
P
P
Shultz
L D
LD
Rajan
T V
TV
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D017178:Brugia malayi / Q000276:immunology*; D017179:Brugia pahangi / Q000276:immunology*; D005368:Filariasis / Q000276:immunology* / Q000517:prevention & control; D005434:Flow Cytometry; D007121:Immunocompetence; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology