B1b lymphocytes confer T cell-independent long-lasting immunity
B1b lymphocytes confer T cell-independent long-lasting immunity
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DOI：
10.1016/j.immuni.2004.06.019
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发表时间：
2004-09-01
期刊：
影响因子：
32.4
通讯作者：
Gerstein, RM
中科院分区：
文献类型：
--
作者：
Alugupalli, KR;Leong, JM;Gerstein, RM
许多微生物病原体利用抗原变异作为一种逃避免疫系统的策略，这给疫苗开发带来了挑战。为了了解针对此类病原体的免疫所需条件，我们研究了赫姆斯疏螺旋体（Borrelia hermsii），一种回归热细菌。我们发现缺乏T细胞、滤泡B细胞、边缘区B细胞或B1a淋巴细胞的小鼠能够消除赫姆斯疏螺旋体菌血症，并对再次感染具有抵抗力。菌血症的消除与B1b淋巴细胞的扩增和持续存在相吻合，并且从康复的野生型或TCR - β×δ（-/-）小鼠中纯化的B1b淋巴细胞赋予了Rag1（-/-）小鼠免疫力。在重建的Rag1（-/-）小鼠中的B1b淋巴细胞通过在细菌攻击时快速产生赫姆斯疏螺旋体特异性IgM而非IgG提供了持久的免疫力。未突变的IgM足以消除赫姆斯疏螺旋体，因为缺乏体细胞高频突变和类别转换重组的AID（-/-）小鼠有效地消除了所有菌血症发作。这些数据表明B1b淋巴细胞能够提供持久的不依赖T细胞的IgM记忆。
Many microbial pathogens employ antigenic variation as a strategy to evade the immune system, posing a challenge in vaccine development. To understand the requirements for immunity against such pathogens, we studied Borrelia hermsii, a relapsing fever bacterium. We found that mice deficient in T, follicular B, marginal zone B, or B1 a lymphocytes resolved B. hermsii bacteremia and became resistant to reinfection. The resolution of bacteremia coincided with an expansion and persistence of B1b lymphocytes, and purified B1b lymphocytes from convalescent wild-type or TCR-betaxdelta(-/-) mice conferred immunity to Rag1(-/-) mice. The B1b lymphocytes in the reconstituted Rag1(-/-) mice provided long-lasting immunity by rapidly generating B. hermsii-specific IgM but not IgG upon bacterial challenge. Unmutated IgM is sufficient to eliminate B. hermsii, because AID(-/-) mice deficient in somatic hypermutation and class switch recombination efficiently resolved all bacteremic episodes. These data demonstrate that B1b lymphocytes can provide long-lasting T cell-independent IgM memory.