Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom.
Blood. 2012 Nov 29;120(23):4552-9. doi: 10.1182/blood-2012-03-417733. Epub 2012 Oct 11.
Antibody-forming cells (AFCs) expressing the chemokine receptor CXCR3 are recruited to sites of inflammation where they help clear pathogens but may participate in autoimmune diseases. Here we identify a mechanism that induces CXCR3 expression by AFC and germinal center (GC) B cells. This happens when CD8 T cells are recruited into CD4 T cell-dependent B-cell responses. Ovalbumin-specific CD4 T cells (OTII) were transferred alone or with ovalbumin-specific CD8 T cells (OTI) and the response to subcutaneous alum-precipitated ovalbumin was followed in the draining lymph nodes. OTII cells alone induce T helper 2-associated class switching to IgG1, but few AFC or GC B cells express CXCR3. By contrast, OTI-derived IFN-γ induces most responding GC B cells and AFCs to express high levels of CXCR3, and diverse switching to IgG2a, IgG2b, with some IgG1. Up-regulation of CXCR3 by GC B cells and AFCs and their migration toward its ligand CXCL10 are shown to depend on B cells' intrinsic T-bet, a transcription factor downstream of the IFN-γR signaling. This model clarifies how precursors of long-lived AFCs and memory B cells acquire CXCR3 that causes their migration to inflammatory foci.
抗体形成细胞（AFC）表达趋化因子受体 CXCR3，被募集到炎症部位，在那里它们有助于清除病原体，但也可能参与自身免疫性疾病。在这里，我们确定了一种诱导 AFC 和生发中心（GC）B 细胞表达 CXCR3 的机制。当 CD8 T 细胞被募集到 CD4 T 细胞依赖性 B 细胞反应中时，就会发生这种情况。单独转导卵清蛋白特异性 CD4 T 细胞（OTII）或与卵清蛋白特异性 CD8 T 细胞（OTI）一起转导，并在引流淋巴结中观察皮下沉淀卵清蛋白的反应。OTII 细胞本身诱导与 Th2 相关的类别转换为 IgG1，但很少有 AFC 或 GC B 细胞表达 CXCR3。相比之下，OTI 衍生的 IFN-γ诱导大多数反应性 GC B 细胞和 AFC 高表达 CXCR3，并向 IgG2a、IgG2b 进行多种转换，同时也有一些 IgG1。GC B 细胞和 AFC 上调 CXCR3 及其向其配体 CXCL10 的迁移被证明依赖于 B 细胞内在的 T-bet，这是 IFN-γR 信号下游的转录因子。该模型阐明了长寿 AFC 和记忆 B 细胞前体如何获得 CXCR3，从而导致它们向炎症焦点迁移。
