B-1a Cells, but Not Marginal Zone B Cells, Are Implicated in the Accumulation of Autoreactive Plasma Cells in Lyn-/- Mice.
B-1a Cells, but Not Marginal Zone B Cells, Are Implicated in the Accumulation of Autoreactive Plasma Cells in Lyn-/- Mice.
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DOI：
10.4049/immunohorizons.2300089
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发表时间：
2024-01-01
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影响因子：
--
通讯作者：
Satterthwaite AB
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文献类型：
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作者：
Ottens K;Schneider J;Satterthwaite AB
缺乏林恩（一种限制B细胞活化的酪氨酸激酶）的小鼠会发生狼疮样自身免疫性疾病，其特征在于脾浆细胞的积聚和自身抗体的产生。林恩-/-小鼠的边缘区（MZ）B细胞数量减少，这是一种富含自身反应性并易于浆细胞分化的B细胞亚群。我们假设这是由于这种潜在致病性B细胞亚群未受抑制的终末分化所致。然而，在林恩−/−小鼠中损害MZ B细胞发育并不能减少浆细胞积累或自身抗体，并且阻止浆细胞分化并不能恢复MZ B细胞数量。相反，当浆细胞分化受损时，林恩−/−小鼠积累了B-1a细胞。与MZ B细胞相似，B-1a细胞倾向于多反应性或弱自身反应性，并为终末分化做好准备。我们的研究结果表明，B-1a细胞，而不是MZ B细胞，是林恩−/−小鼠自身反应性浆细胞池的贡献者。
Mice deficient in Lyn, a tyrosine kinase that limits B cell activation, develop a lupus-like autoimmune disease characterized by the accumulation of splenic plasma cells and the production of autoantibodies. Lyn−/− mice have reduced numbers of marginal zone (MZ) B cells, a B cell subset that is enriched in autoreactivity and prone to plasma cell differentiation. We hypothesized that this is due to unchecked terminal differentiation of this potentially pathogenic B cell subpopulation. However, impairing MZ B cell development in Lyn−/− mice did not reduce plasma cell accumulation or autoantibodies, and preventing plasma cell differentiation did not restore MZ B cell numbers. Instead, Lyn−/− mice accumulated B-1a cells when plasma cell differentiation was impaired. Similar to MZ B cells, B-1a cells tend to be polyreactive or weakly autoreactive and are primed for terminal differentiation. Our results implicate B-1a cells, but not MZ B cells, as contributors to the autoreactive plasma cell pool in Lyn−/− mice.