Regulation of CXCR3 and CXCR4 expression during terminal differentiation of memory B cells into plasma cells
Regulation of CXCR3 and CXCR4 expression during terminal differentiation of memory B cells into plasma cells
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DOI：
10.1182/blood-2004-08-2992
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发表时间：
2005-05-15
期刊：
影响因子：
20.3
通讯作者：
Manz, RA
中科院分区：
文献类型：
--
作者：
Muehlinghaus, G;Cigliano, L;Manz, RA
在记忆免疫应答中形成的免疫球蛋白G（IgG） - 浆细胞前体上表达的C - X - C基序趋化因子受体3（CXCR3）和CXCR4是这些细胞归巢的关键调节因子。在此，我们研究了人类记忆B细胞分化为浆细胞过程中这些趋化因子受体表达的调控。我们发现CXCR3在CD27（ - ）初始B细胞上不表达，但在一部分记忆B细胞上表达，且优先在共表达IgG1的记忆B细胞上表达。在分化为浆细胞前体时，CXCR3（ + ）记忆B细胞维持这种趋化因子受体的表达。CXCR3（ - ）记忆B细胞仅在受到干扰素γ（IFN - γ）共刺激时会上调CXCR3，并朝着其配体的浓度梯度迁移，而白细胞介素4（IL - 4）、IL - 1β、IL - 6、干扰素α（IFN - α）、干扰素β（IFN - β）或肿瘤坏死因子α（TNF - α）则无此作用。相反，CXCR4（ - ）B细胞分化为浆细胞通常伴随着CXCR4表达的诱导。这些结果表明，浆细胞前体上缺乏CXCR4表达不是浆细胞归巢的限制因素，并且在人类1型辅助性T细胞（Th1）偏向的免疫应答中，干扰素γ可诱导记忆B细胞和浆细胞前体上CXCR3的表达。一旦在记忆B细胞中被诱导，CXCR3的表达就会成为个体细胞记忆的一部分。（c）2005年美国血液学会版权所有。
C-X-C motif chemokine receptor 3 (CXCR3) and CXCR4 expressed on immunoglobulin G (IgG)-plasma-cell precursors formed in memory immune responses are crucial modulators of the homing of these cells. Here, we studied the regulation of the expression of these chemokine receptors during the differentiation of human memory B cells into plasma cells. We show that CXCR3 is absent on CD27(-) naive B cells but is expressed on a fraction of memory B cells, preferentially on those coexpressing IgG1. On differentiation into plasma-cell precursors, CXCR3(+) memory B cells maintain the expression of this chemokine receptor. CXCR3(-) memory B cells up-regulate CXCR3 and migrate toward concentration gradients of its ligands only when costimulated with interferon gamma (IFN-gamma), but not interleukin 4 (IL-4), IL-1 beta, IL-6, IFN-alpha, IFN-beta, or tumor necrosis factor a (TNF-alpha). In contrast, the differentiation of CXCR4(-) B cells into plasma cells is generally accompanied by the induction of CXCR4 expression. These results show that lack of CXCR4 expression on plasma-cell precursors is not a limiting factor for plasma-cell homing and that the expression of CXCR3 on memory B cells and plasma-cell precursors is induced by IFN-gamma, provided in human T helper type 1 (Th1)-biased immune responses. Once induced in memory B cells, CXCR3 expression remains part of the individual cellular memory. (c) 2005 by The American Society of Hematology.