Tissue Distribution and Dependence of Responsiveness of Human Antigen-Specific Memory B Cells
Tissue Distribution and Dependence of Responsiveness of Human Antigen-Specific Memory B Cells
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DOI：
10.4049/jimmunol.1302783
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发表时间：
2014-04-01
影响因子：
4.4
通讯作者：
Doerner, Thomas
中科院分区：
文献类型：
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作者：
Giesecke, Claudia;Froelich, Daniela;Doerner, Thomas
记忆B细胞（mBCs）是免疫记忆的关键，但它们在淋巴器官中的分布以及它们对mBC功能的个体作用在很大程度上仍然未知。本研究表征了人（ag特异性）mBCs在外周血（PB）、脾脏、扁桃体和骨髓中的分布和表型。我们发现脾脏含有最多的mBCs，其次是扁桃体、BM和PB，并且我们发现与更高成熟度相关的标记物的表达没有重大差异。对破伤风类毒素特异性（TT+） mBCs的分布检测显示其在稳定状态下存在于PB中，但绝对数量表明其最大的储存库在脾脏，其次是扁桃体。为了探索这两种组织在维持反应性B细胞记忆中的作用，我们对对照组和脾切除和扁桃体切除的个体重新接种了TT疫苗。所有供体组PB中出现的抗TT IgG、TT+浆细胞和TT+ mBCs具有可比性，且TT+浆细胞的分子特征相似。总之，人的mBC通过PB循环并存在于不同的淋巴器官中，这些器官并不反映不同的mBC成熟阶段。脾脏和扁桃体虽然拥有最多的整体和TT+ mBCs，但对于保持对继发性抗原攻击的足够反应性似乎是必不可少的。
Memory B cells (mBCs) are a key to immunologic memory, yet their distribution within lymphoid organs and the individual role of these for mBC functionality remain largely unknown. This study characterized the distribution and phenotype of human (Ag-specific) mBCs in peripheral blood (PB), spleen, tonsil, and bone marrow. We found that the spleen harbors most mBCs, followed by tonsils, BM, and PB, and we detected no major differences in expression of markers associated with higher maturity. Testing the distribution of tetanus toxoid-specific (TT+) mBCs revealed their presence in PB during steady state, yet absolute numbers suggested their largest reservoir in the spleen, followed by tonsils. To explore the role of both tissues in the maintenance of reactive B cell memory, we revaccinated controls and splenectomized and tonsillectomized individuals with TT. All donor groups exhibited comparable emergence of anti-TT IgG, TT+ plasma cells, and TT+ mBCs in the PB, together with similar molecular characteristics of TT+ plasma cells. In summary, human mBCs recirculate through PB and reside in different lymphoid organs that do not reflect different mBC maturity stages. The spleen and tonsil, although harboring the largest number of overall and TT+ mBCs, appear to be dispensable to preserve adequate responsiveness to secondary antigenic challenge.