Absence of marginal zone B cells in Pyk-2-deficient mice defines their role in the humoral response
Absence of marginal zone B cells in Pyk-2-deficient mice defines their role in the humoral response
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DOI：
10.1038/76882
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发表时间：
2000-07-01
影响因子：
30.5
通讯作者：
Ravetch, JV
中科院分区：
文献类型：
--
作者：
Guinamard, R;Okigaki, M;Ravetch, JV
淋巴器官包含由淋巴细胞、髓细胞和基质细胞组成的特殊微观解剖结构，这些结构对产生有效的适应性免疫应答至关重要。尽管这些特殊结构的存在已为人所知一个多世纪，但产生它们的发育信号以及这些结构在免疫应答中的具体作用在很大程度上仍然不清楚。由于边缘区B细胞（MZB细胞）位于边缘窦附近，它们是最早接触血源性抗原的细胞群之一，并且被认为在宿主防御细菌病原体方面具有关键作用。在此我们证明，酪氨酸激酶（Pyk - 2）的缺乏会导致MZB细胞产生的细胞自主性缺陷。在对重复多糖抗原（非T细胞依赖型II类（TI - II））的应答中，Pyk - 2缺陷型小鼠表现出IgM、IgG3和IgG2a产生的显著抑制。此外，已证明补体受体的参与对于多糖抗原特异性靶向MZB细胞是必要的。这些结果表明了通过补体偶联介导的先天性免疫应答是如何被MZB细胞转化为适应性应答的，并为针对多糖抗原的体液应答的T细胞非依赖性提供了一种潜在机制。
The lymphoid organs contain specialized microanatomic structures composed of lymphoid, myeloid and stromal cells that are vital to the generation of an effective adaptive immune response,Although the existence of these specialized structures has been known for over a century, the developmental signals that generate them and the specific roles of these structures in the immune response have remained largely elusive, Because of their position adjacent to the marginal sinuses, marginal zone B (MZB) cells are amongst the first population of cells seen by blood born antigens and are presumed to have a critical role in host defense against bacterial pathogens. Here we demonstrate that a deficiency of the tyrosine kinase (Pyk-2) results in a cell autonomous defect of MZB cell production. In response to repetitive polysaccharide antigens (T-independent type II (TI-II)) Pyk-2-deficient mice displayed marked suppression of IgM, IgG3 and IgG2a production. Furthermore, complement receptor engagement proved necessary for the specific targeting of polysaccharide antigens to MZB cells,These results suggest how innate immune responses mediated through complement coupling are translated into an adaptive response by MZB cells, and provide a potential mechanism for the T cell independence of humoral responses to polysaccharide antigens.