A role for B cells in resistance to Cryptococcus neoformans in mice.
The role of B cells in immunity to Cryptococcus neoformans was investigated. Genetically targeted, B-cell-deficient mice (mu Mt) examined at various times after intravenous infection with C. neoformans 184 had lung and brain yeast burdens that were equivalent to tissue burdens in control B-cell-sufficient mice. Both B-cell-deficient and B-cell-sufficient control mice were effectively vaccinated by a sublethal intratracheal instillation of strain 184 yeast against a systemic infection with the C. neoformans strain carrying ura5; vaccinated control and vaccinated B-cell-deficient mice had equivalent brain and lung burdens of the ura5 strain 10 days after intravenous rechallenge. Additionally, B-cell-deficient and B-cell-sufficient vaccinated mice survived an intravenous rechallenge with a dose of yeast cells which is normally lethal for unimmunized mice. In further studies of the role of B cells in murine cryptococcosis, SCID mice were reconstituted with lymphocytes from B-cell-deficient and B-cell-sufficient mice. SCID mice reconstituted with lymphocytes from vaccinated B-cell-deficient animals failed to express effective adoptive immunity to C. neoformans brain infection. In contrast, SCID mice reconstituted with lymphocytes from vaccinated B-cell-sufficient mice had 10-fold fewer yeast cells in their brains than did uninfused SCID controls. However, SCID mice given lymphocytes from B-cell-deficient immune donors had fewer yeast cells in their lungs than did uninfused controls. Fewer CD4+ lymphocytes were recovered at 7 and 11 days after infection from the peripheral blood and spleens of SCID mice reconstituted with lymphocyte suspensions from B-cell-deficient animals than from the peripheral blood and spleens of SCID mice reconstituted with suspensions from B-cell-sufficient control donors. These data suggest that B cells can play an important role in host defense against Cryptococcus in the brain under conditions in which T-cell-mediated immunity is impaired.
Aguirre
K M
KM
Trudeau Institute, Saranac Lake, New York 12983, USA.
Johnson
L L
LL
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation; D003453:Cryptococcosis / Q000276:immunology* / Q000517:prevention & control; D003455:Cryptococcus neoformans / Q000276:immunology*; D007113:Immunity, Innate; D007700:Kinetics; D008168:Lung / Q000276:immunology / Q000382:microbiology; D017710:Lymphocyte Transfusion; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID