TY - JOUR
T1 - Clearance of Pneumocystis carinii in mice is dependent on B cells but not on P. carinii-specific antibody
AU - Lund, Frances E.
AU - Schuer, Kevin
AU - Hollifield, Melissa
AU - Randall, Troy D.
AU - Garvy, Beth A.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - 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 FcγRI and III (FcγRKO), 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 FcγR, since C3-deficient and C3-depleted FcγRKO mice were still able to clear P. carinii. Finally, μMT 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.
AB - 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 FcγRI and III (FcγRKO), 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 FcγR, since C3-deficient and C3-depleted FcγRKO mice were still able to clear P. carinii. Finally, μMT 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.
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U2 - 10.4049/jimmunol.171.3.1423
DO - 10.4049/jimmunol.171.3.1423
M3 - Article
C2 - 12874234
AN - SCOPUS:0042847159
VL - 171
SP - 1423
EP - 1430
IS - 3
ER -