Clearance of Pneumocystis carinii in mice is dependent on B cells but not on P carinii-specific antibody.
Both CD4(+) T cells and B cells are critical for defense against Pneumocystis carinii infection; however, the mechanism by which B cells mediate protection is unknown. We show that P. carinii-specific IgM is not sufficient to mediate clearance of P. carinii from the lungs since CD40-deficient mice produced normal levels of specific IgM, but were unable to clear the organisms. Using chimeric mice in which the B cells were deficient in CD40 (CD40KO chimeras) we found that clearance of P. carinii infection is delayed compared with wild-type controls. These CD40KO chimeric mice produced normal levels of P. carinii-specific IgM, but did not produce class-switched IgG or IgA. Similarly, clearance of P. carinii was delayed in mice deficient in FcgammaRI and III (FcgammaRKO), indicating that P. carinii-specific IgG partially mediates opsonization and clearance of P. carinii. Opsonization of organisms by complement did not compensate for the lack of specific IgG or FcgammaR, since C3-deficient and C3-depleted FcgammaRKO mice were still able to clear P. carinii. Finally, micro MT and CD40KO chimeric mice had reduced numbers of activated CD4(+) T cells in the lungs and lymph nodes compared with wild-type mice, suggesting that B cells are important for activation of T cells in response to P. carinii. Together these data indicate that P. carinii-specific IgG plays an important, but not critical, role in defense against P. carinii. Moreover, these data suggest that B cells also mediate host defense against P. carinii by facilitating CD4(+) T cell activation or expansion.
Lund
Frances E
FE
Trudeau Institute, Saranac Lake, NY 12983, USA.
Schuer
Kevin
K
Hollifield
Melissa
M
Randall
Troy D
TD
Garvy
Beth A
BA
D000818:Animals; D000908:Antibodies, Fungal / Q000502:physiology*; D000918:Antibody Specificity; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001980:Bronchi; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D023201:CD40 Ligand / Q000378:metabolism / Q000502:physiology; D002678:Chimera / Q000235:genetics / Q000276:immunology; D003165:Complement System Proteins / Q000172:deficiency / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D011010:Pneumocystis / Q000254:growth & development* / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000235:genetics / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control*; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics; D014132:Trachea
D000908:Antibodies, Fungal; D019013:CD40 Antigens; D017452:Receptors, IgG; D023201:CD40 Ligand; D003165:Complement System Proteins