Lund Frances E, Schuer Kevin, Hollifield Melissa, Randall Troy D, Garvy Beth A
Trudeau Institute, Saranac Lake, NY 12983, USA.
J Immunol. 2003 Aug 1;171(3):1423-30. doi: 10.4049/jimmunol.171.3.1423.
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.
CD4(+) T细胞和B细胞对于抵御卡氏肺孢子虫感染都至关重要；然而，B细胞介导保护作用的机制尚不清楚。我们发现，卡氏肺孢子虫特异性IgM不足以介导从肺部清除卡氏肺孢子虫，因为CD40缺陷小鼠产生正常水平的特异性IgM，但无法清除病原体。利用B细胞缺乏CD40的嵌合小鼠（CD40KO嵌合体），我们发现与野生型对照相比，卡氏肺孢子虫感染的清除被延迟。这些CD40KO嵌合小鼠产生正常水平的卡氏肺孢子虫特异性IgM，但不产生类别转换的IgG或IgA。同样，在缺乏FcγRI和III的小鼠（FcγRKO）中，卡氏肺孢子虫的清除也被延迟，这表明卡氏肺孢子虫特异性IgG部分介导了卡氏肺孢子虫的调理作用和清除。补体对病原体的调理作用并不能弥补特异性IgG或FcγR的缺乏，因为C3缺陷和C3耗竭的FcγRKO小鼠仍然能够清除卡氏肺孢子虫。最后，与野生型小鼠相比，微型MT和CD40KO嵌合小鼠肺部和淋巴结中活化的CD4(+) T细胞数量减少，这表明B细胞对于响应卡氏肺孢子虫激活T细胞很重要。这些数据共同表明，卡氏肺孢子虫特异性IgG在抵御卡氏肺孢子虫的过程中发挥重要但非关键的作用。此外，这些数据表明B细胞还通过促进CD4(+) T细胞活化或扩增来介导宿主对卡氏肺孢子虫的防御。
