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

Author

Listed:
  • Hai Qi

    (Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Jennifer L. Cannons

    (Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Frederick Klauschen

    (Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Pamela L. Schwartzberg

    (Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA)

  • Ronald N. Germain

    (Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA)

Abstract

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.

Suggested Citation

  • Hai Qi & Jennifer L. Cannons & Frederick Klauschen & Pamela L. Schwartzberg & Ronald N. Germain, 2008. "SAP-controlled T–B cell interactions underlie germinal centre formation," Nature, Nature, vol. 455(7214), pages 764-769, October.
    • Handle: RePEc:nat:nature:v:455:y:2008:i:7214:d:10.1038_nature07345
    DOI: 10.1038/nature07345
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    Cited by:

    1. Yuande Wang & Yuhe Quan & Junming He & Shasha Chen & Zhongjun Dong, 2024. "SLAM-family receptors promote resolution of ILC2-mediated inflammation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Marta Iborra-Pernichi & Jonathan Ruiz García & María Velasco de la Esperanza & Belén S. Estrada & Elena R. Bovolenta & Claudia Cifuentes & Cristina Prieto Carro & Tamara González Martínez & José Garcí, 2024. "Defective mitochondria remodelling in B cells leads to an aged immune response," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Fangming Zhu & Ryan J. McMonigle & Andrew R. Schroeder & Xianyou Xia & David Figge & Braxton D. Greer & Edahí González-Avalos & Diego O. Sialer & Yin-Hu Wang & Kelly M. Chandler & Adam J. Getzler & Em, 2023. "Spatiotemporal resolution of germinal center Tfh cell differentiation and divergence from central memory CD4+ T cell fate," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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