Macrophages control the retention and trafficking of B lymphocytes in the splenic marginal zone.

Macrophages control the retention and trafficking of B lymphocytes in the splenic marginal zone.
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DOI:
10.1084/jem.20030684
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发表时间:
2003-07-21
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Ravetch JV
Ravetch JV
中科院分区:
其他
文献类型:
--
作者:
Karlsson MC;Guinamard R;Bolland S;Sankala M;Steinman RM;Ravetch JV

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脾脏边缘区是一个精确有序的区域,包含专门的B淋巴细胞和巨噬细胞亚群。负信号肌醇磷酸酶sh2 -含肌醇-5-磷酸酶1 (SHIP)的破坏,导致边缘区B细胞(MZBs)的损失,边缘区巨噬细胞(MZMOs)重组到脾脏的红髓。这种原发性巨噬细胞缺陷,通过选择性地消耗髓细胞中的SHIP显示,MZMOs是MZBs保留所特别需要的。在SHIP/Bruton’s tyrosine kinase (Btk)双敲除小鼠中,MZMO表型恢复,从而确定Btk激活途径是SHIP调控的重要组分。此外,我们还发现了MZMOs和MZBs上的MARCO清道夫受体之间的直接相互作用。这种相互作用的激活或破坏导致MZB向卵泡迁移。在对金黄色葡萄球菌产生反应后,我们进一步研究了MZMOs的迁移,金黄色葡萄球菌诱导MZMOs迁移到红髓,而MZBs迁移到滤泡区。因此,边缘区是一个动态结构,其中B细胞的保留和运输需要特定的巨噬细胞- B细胞相互作用。
The marginal zone of the spleen is a precisely ordered region that contains specialized subsets of B lymphocytes and macrophages. Disruption of the negative signaling inositol phosphatase, SH2-containing inositol-5-phosphatase 1 (SHIP), results in the loss of marginal zone B cells (MZBs) with reorganization of marginal zone macrophages (MZMOs) to the red pulp of the spleen. This primary macrophage defect, as revealed by selectively depleting SHIP in myeloid cells shows that MZMOs are specifically required for the retention of MZBs. The MZMO phenotype was reverted in SHIP/Bruton's tyrosine kinase (Btk) double knockout mice, thus identifying the Btk activating pathway as an essential component being regulated by SHIP. Furthermore, we identified a direct interaction between the MARCO scavenger receptor on MZMOs and MZBs. Activation or disruption of this interaction results in MZB migration to the follicle. The migration of the MZMOs was further studied after the response to Staphylococcus aureus, which induced MZMOs to move into the red pulp while MZBs migrated into the follicular zone. The marginal zone is therefore a dynamic structure in which retention and trafficking of B cells requires specific macrophage–B cell interactions.
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