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.