SAP-controlled T-B cell interactions underlie germinal centre formation

Article

关键词: LINKED LYMPHOPROLIFERATIVE-DISEASE;    HUMORAL IMMUNITY;    DENDRITIC CELLS;    IN-VIVO;    LYMPH-NODES;    CYTOKINE REGULATION;    ANTIBODY-RESPONSES;    GENE-PRODUCT;    ACTIVATION;    INFECTION;   

DOI  :  10.1038/nature07345

来源: SCIE

【 摘 要 】

Generation of long- term antibody- mediated immunity depends on the germinal centre reaction, which requires cooperation between antigen- specific T and B lymphocytes. In human X- linked lymphoproliferative disease and its gene- targeted mouse model, loss- of- function mutations in signalling lymphocyte activation molecule- associated protein ( SAP, encoded by SH2D1a) cause a profound defect in germinal centre formation by an as yet unknown mechanism. Here, using two- photon intravital imaging, we show that SAP deficiency selectively impairs the ability of CD4(+) T cells to stably interact with cognate B cells but not antigen- presenting dendritic cells. This selective defect results in a failure of antigen- specific B cells to receive adequate levels of contact- dependent T- cell help to expand normally, despite Sap(-/-) T cells exhibiting the known characteristics of otherwise competent helper T cells. Furthermore, the lack of stable interactions with B cells renders Sap(-/-) T cells unable to be efficiently recruited to and retained in a nascent germinal centre to sustain the germinal centre reaction. These results offer an explanation for the germinal centre defect due to SAP deficiency and provide new insights into the bi- directional communication between cognate T and B cells in vivo.

【 授权许可】

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