The resolution of relapsing fever borreliosis requires IgM and is concurrent with expansion of B1b lymphocytes
The resolution of relapsing fever borreliosis requires IgM and is concurrent with expansion of B1b lymphocytes
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DOI：
10.4049/jimmunol.170.7.3819
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发表时间：
2003-04-01
影响因子：
4.4
通讯作者：
Leong, JM
中科院分区：
文献类型：
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作者：
Alugupalli, KR;Gerstein, RM;Leong, JM
病原体清除率是发病率和死亡率的关键决定因素。我们试图描述免疫反应的特征，该反应负责快速清除由回归热、细菌、赫氏疏螺旋体引起的个别菌血症发作。 SCID 或 Rag(-/-) 小鼠无法解决赫氏芽胞杆菌感染，表明 T 和/或 B 细胞发挥着关键作用。缺乏T细胞的TCR-/-小鼠和缺乏T细胞和滤泡B细胞但缺乏B1细胞和脾边缘区(MZ) B细胞的IL-7(-/-)小鼠能够有效清除赫氏芽孢杆菌。这些发现表明，B1 细胞和/或 MZ B 细胞（已知参与快速、不依赖 T 细胞的反应的两种 B 细胞亚群）可能参与其中。脾切除小鼠对中度菌血症发作的有效解决表明，MZ B 细胞在清除这种细菌中并不起主要作用。相比之下，缺乏B1细胞的xid小鼠比野生型小鼠遭受更严重的菌血症发作。 B1 细胞对于清除赫氏伯克霍尔德氏菌至关重要的假设得到了受感染 xid 小鼠中 B1b（即 IgM（高）、IgD（-/低）、Mac1（+）CD23（-）和 CD5（-））细胞亚群的选择性扩增的进一步支持，这与感染的最终解决相一致。最后，选择性地无法分泌 IgM（B1 细胞产生的主要同种型）的小鼠完全无法清除赫氏疏螺旋体。这些结果共同支持了这样的模型：B1b 细胞产生控制和解决回归热疏螺旋体病所需的 T 依赖性 IgM。
The rate of pathogen clearance is a critical determinant of morbidity and mortality. We sought to characterize the immune response responsible for the remarkably rapid clearance of individual episodes of bacteremia caused by the relapsing fever, bacterium, Borrelia hermsii. SCID or Rag(-/-) mice were incapable of resolving B. hermsii infection, indicating a critical role for T and/or B cells. TCR-/- mice, which lack T cells, and IL-7(-/-) mice, which are deficient in both T cells and follicular B cells, but not in B1 cells and splenic marginal zone (MZ) B cells, efficiently cleared B. hermsii. These findings suggested that B1 cells and/or MZ B cells, two B cell subsets that are known to participate in rapid, T-independent responses, might be involved. The efficient resolution of the episodes of moderate level bacteremia by splenectomized mice suggested that MZ B cells do not play the primary role in clearance of this bacterium. In contrast, xid mice, which are deficient in B1 cells, suffered more severe episodes of bacteremia than wild-type mice. The hypothesis that B1 cells are critical for clearance of B. hermsii was further supported by a selective expansion of the B1b (i.e., IgM(high), IgD(-/low), Mac1(+) CD23(-), and CD5(-)) cell subset in infected xid mice, which coincided with the eventual resolution of infection. Finally, mice selectively incapable of secreting IgM, the dominant isotype produced by B1 cells, were completely unable to clear B. hermsii. Together these results support the model that B1b cells generate the T-independent IgM required for the control and resolution of relapsing fever borreliosis.