Developmental switches in chemokine response profiles during B cell differentiation and maturation.
Developmental switches in chemokine response profiles during B cell differentiation and maturation.
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DOI：
10.1084/jem.191.8.1303
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发表时间：
2000-04-17
影响因子：
15.3
通讯作者：
Butcher, E C
中科院分区：
文献类型：
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作者：
Bowman, E P;Campbell, J J;Soler, D;Dong, Z;Manlongat, N;Picarella, D;Hardy, R R;Butcher, E C
发育中的B细胞对趋化因子的反应和趋化因子受体的表达发生了巨大的变化。骨髓前原B细胞（AA 4.1 +/自然杀伤1.1-A级分细胞）和能够在白细胞介素7和flt 3配体存在下产生原B集落的细胞迁移至胸腺表达趋化因子（TECK），这是B细胞发育后期丧失的一种反应。吸引B细胞的趋化因子1（BCA-1）应答与CXC趋化因子受体（CXCR）5表达相关，首先由前B细胞亚群显示，在前B细胞中丢失，然后在从骨髓排出之前和之后重新获得。所有外周B细胞亚群，包括滤泡和生发中心以及边缘区和腹膜B1 B细胞，对BCA-1有反应，这意味着对这种滤泡趋化因子的反应不足以预测滤泡定位。对CC趋化因子受体（CCR）7配体次级淋巴组织化学引诱物（SLC）和巨噬细胞炎性蛋白（MIP）-3β的反应（涉及归巢至淋巴组织）在B细胞从骨髓中退出之前上调，但在外周中进一步增加，并由所有外周B细胞共享。相反，对MIP-3α的反应性和CCR 6的表达仅在迁移至外周后和成熟进入再循环B细胞池期间获得。在B细胞分化的所有阶段均观察到对基质细胞衍生因子1α的趋化性。因此，趋化因子反应的独特模式可能有助于定义发育中的B细胞群，并指导它们在骨髓中的成熟和向外周的迁移。
Developing B cells undergo dramatic changes in their responses to chemoattractant cytokines (chemokines) and in expression of chemokine receptors. Bone marrow pre–pro-B cells (AA4.1+/natural killer 1.1− Fraction A cells) and cells capable of generating pro-B colonies in the presence of interleukin 7 and flt3 ligand migrate to thymus-expressed chemokine (TECK), a response lost in later stages of B cell development. B cell–attracting chemokine 1 (BCA-1) responses correlate with CXC chemokine receptor (CXCR)5 expression, are first displayed by a pro-B cell subset, are lost in pre-B cells, and then are regained just before and after egress from the marrow. All peripheral B cell subsets, including follicular and germinal center as well as marginal zone and peritoneal B1 B cells, respond to BCA-1, implying that responsiveness to this follicular chemokine is not sufficient to predict follicle localization. Responses to the CC chemokine receptor (CCR)7 ligands secondary lymphoid tissue chemoattractant (SLC) and macrophage inflammatory protein (MIP)-3β, implicated in homing to lymphoid tissues, are upregulated before B cell exit from the marrow, but increase further in the periphery and are shared by all peripheral B cells. In contrast, responsiveness to MIP-3α and expression of CCR6 are acquired only after emigration to the periphery and during maturation into the recirculating B cell pool. Chemotaxis to stromal cell–derived factor 1α is observed at all stages of B cell differentiation. Thus, unique patterns of chemokine responses may help define developing B cell populations and direct their maturation in the marrow and migration to the periphery.