Homing and Adhesion Patterns Determine the Cellular Composition of the Bone Marrow Plasma Cell Niche
Homing and Adhesion Patterns Determine the Cellular Composition of the Bone Marrow Plasma Cell Niche
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DOI：
10.4049/jimmunol.1103169
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发表时间：
2012-02-01
影响因子：
4.4
通讯作者：
Siegrist, Claire-Anne
中科院分区：
文献类型：
--
作者：
Belnoue, Elodie;Tougne, Chantal;Siegrist, Claire-Anne
根据普遍持有的概念，骨髓（BM）中的浆细胞（PC）寿命取决于它们对生存小生境的访问。这些被认为存在于托儿所细胞类型中，通过分泌PC存活因子来支持PC。为了更好地定义PC生存壁龛及其功能，我们将可追踪的Blimp-1-（GFP）PC过继转移到缺乏增殖诱导配体（APRIL）、IL-6或巨噬细胞迁移抑制因子的受体小鼠中。转移的BMPC优先与Ly-6C（高）单核细胞（标准化共定位指数：9.84）、嗜酸性粒细胞（4.29）和巨核细胞（2.12）相关。虽然APRIL是必不可少的BMPC的生存，PC招募到附近的托儿所细胞是不受影响的APRIL缺陷小鼠，质疑的概念，即相同的因素占吸引/保留的PC，因为他们的本地生存。相反，与BMPC共定位的顺序（单核细胞>嗜酸性粒细胞>巨核细胞）反映了这些细胞CXCR 4、VLA-4和LFA-1的相对表达，这些分子是引导/保留BM中PC的归巢和粘附分子。这表明了一种情况，其中BMPC小生境的细胞组成由CXCL 12丰富的网状对接细胞上的吸引/保留的共同模式定义。因此，PC被引导在功能性BM小生境中与造血CXCR 4（+）VLA-4（+）LFA-1（+）保育细胞缔合，其提供PC存活因子。免疫学杂志，2012，188：1283-1291。
According to commonly held concepts, plasma cell (PC) longevity in bone marrow (BM) depends upon their access to survival niches. These are thought to exist in nursery cell types, which support PCs by secreting PC survival factors. To better define PC survival niches and their functioning, we adoptively transferred traceable Blimp-1-(GFP) PCs into recipient mice lacking a proliferation-inducing ligand (APRIL), IL-6, or macrophage migration inhibitory factor. Transferred BMPCs were preferentially associated with Ly-6C(high) monocytes (normalized colocalization index: 9.84), eosinophils (4.29), and megakaryocytes (2.12). Although APRIL was essential for BMPC survival, PC recruitment into the proximity of nursery cells was unimpaired in APRIL-deficient mice, questioning the concept that the same factors account for attraction/retention of PCs as for their local survival. Rather, the order of colocalization with BMPCs (monocytes > eosinophils > megakaryocytes) reflected these cells' relative expression of CXCR4, VLA-4, and LFA-1, the homing and adhesion molecules that direct/retain PCs in the BM. This suggests a scenario wherein the cellular composition of the BMPC niche is defined by a common pattern of attraction/retention on CXCL12-abundant reticular docking cells. Thereby, PCs are directed to associate in a functional BM niche with hematopoietic CXCR4(+)VLA-4(+)LFA-1(+) nursery cells, which provide PC survival factors. The Journal of Immunology, 2012, 188: 1283-1291.