Gene-targeted mice lacking B cells are unable to eliminate a blood stage malaria infection.
Mice deficient of mature B cells due to a targeted disruption of the transmembrane exon of the Ig mu-chain gene (mu-MT mice) can reduce a primary acute infection with the malaria parasite Plasmodium chabaudi chabaudi (AS strain) to low levels but are unable to eliminate parasites and instead develop chronic relapsing parasitemias. This model of B cell deficiency confirms previous findings using anti-mu-treated mice that B cells are required for final parasite clearance. Injection of B cells from immune donors into chronically infected mu-MT mice enabled them to clear their infection within 1 wk. When mu-MT mice that had been cured of their malaria infection by treatment with chloroquine were rechallenged with P. c. chabaudi (AS) they developed secondary infections of a magnitude similar to a primary infection, in contrast to wild-type mice in which a secondary challenge results only in a transient low patent parasitemia. These results suggest that B cell-dependent mechanisms play a crucial role in immunity to secondary infections. There is a pronounced expansion of gamma delta cells in the spleen of chronically infected mu-MT mice. After clearance of parasites in mu-MT mice either after adoptive transfer of immune B cells or by treatment with chloroquine, gamma delta T cells returned to levels observed in wild-type mice. This suggests that the expansion of gamma delta cells observed in mu-MT mice is due to the chronic persistence of parasites, rather than to the lack of B cells.
von der Weid
T
T
Max-Planck Institute for Immunobiology, Freiburg, Germany.
Honarvar
N
N
Langhorne
J
J
D000818:Animals; D000913:Antibodies, Protozoan / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D018390:Gene Targeting; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D016219:Immunotherapy, Adoptive; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008288:Malaria / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018512:Parasitemia / Q000235:genetics / Q000276:immunology; D016788:Plasmodium chabaudi / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013997:Time Factors
D000913:Antibodies, Protozoan; D007148:Immunoglobulin mu-Chains; D016692:Receptors, Antigen, T-Cell, gamma-delta