Department of Immunology, School of Chemical Sciences, National University of Córdoba, Córdoba, Argentina.
PLoS Negl Trop Dis. 2010 May 4;4(5):e679. doi: 10.1371/journal.pntd.0000679.
B cells and antibodies are involved not only in controlling the spread of blood circulating Trypanosoma cruzi, but also in the autoreactive manifestations observed in Chagas disease. Acute infection results in polyclonal B cell activation associated with hypergammaglobulinemia, delayed specific humoral immunity and high levels of non-parasite specific antibodies. Since TNF superfamily B lymphocyte Stimulator (BAFF) mediates polyclonal B cell response in vitro triggered by T. cruzi antigens, and BAFF-Tg mice show similar signs to T. cruzi infected mice, we hypothesized that BAFF can mediate polyclonal B cell response in experimental Chagas disease.
METHODOLOGY/PRINCIPAL FINDINGS: BAFF is produced early and persists throughout the infection. To analyze BAFF role in experimental Chagas disease, Balb/c infected mice were injected with BR3:Fc, a soluble receptor of BAFF, to block BAFF activity. By BAFF blockade we observed that this cytokine mediates the mature B cell response and the production of non-parasite specific IgM and IgG. BAFF also influences the development of antinuclear IgG and parasite-specific IgM response, not affecting T. cruzi-specific IgG and parasitemia. Interestingly, BAFF inhibition favors the parasitism in heart.
CONCLUSIONS/SIGNIFICANCE: Our results demonstrate, for the first time, an active role for BAFF in shaping the mature B cell repertoire in a parasite infection.
B 细胞和抗体不仅参与控制血液循环中 Trypanosoma cruzi 的扩散，还参与恰加斯病中观察到的自身免疫表现。急性感染导致多克隆 B 细胞活化，伴有高丙种球蛋白血症、延迟特异性体液免疫和高水平的非寄生虫特异性抗体。由于 TNF 超家族 B 淋巴细胞刺激因子（BAFF）在体外介导 T. cruzi 抗原触发的多克隆 B 细胞反应，并且 BAFF-Tg 小鼠表现出与 T. cruzi 感染小鼠相似的迹象，我们假设 BAFF 可以介导实验性恰加斯病中的多克隆 B 细胞反应。
方法/主要发现：BAFF 早期产生并在整个感染过程中持续存在。为了分析 BAFF 在实验性恰加斯病中的作用，用 BR3：Fc（BAFF 的可溶性受体）注射感染 Balb/c 小鼠以阻断 BAFF 活性。通过 BAFF 阻断，我们观察到这种细胞因子介导成熟 B 细胞反应以及非寄生虫特异性 IgM 和 IgG 的产生。BAFF 还影响抗核 IgG 和寄生虫特异性 IgM 反应的发展，而不影响 T. cruzi 特异性 IgG 和寄生虫血症。有趣的是，BAFF 抑制有利于心脏中的寄生虫定殖。
结论/意义：我们的研究结果首次表明，BAFF 在寄生虫感染中塑造成熟 B 细胞库方面发挥了积极作用。
