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Clearance of Pneumocystis carinii in Mice Is Dependent on B Cells But Not on P. carinii-Specific Antibody ¹

Frances E. Lund^*, Kevin Schuer, Melissa Hollifield, Troy D. Randall^* and Beth A. Garvy^2,,,

^* Trudeau Institute, Saranac Lake, NY 12983; Departments of Internal Medicine and Microbiology, Immunology, and Molecular Genetics, University of Kentucky and Veterans Administration Medical Center, Lexington, KY 40536

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 FcRI and III (FcRKO), 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 FcR, since C3-deficient and C3-depleted FcRKO 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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