Cited by 653T-cell and B-cell ImmunologyImmunodeficiency and Autoimmune DisordersImmune Response and Inflammation

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

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Qi, Hai, Cannons, Jennifer L., Klauschen, Frederick, Schwartzberg, Pamela L., Germain, Ronald N.·2008·Nature

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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.

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Follicular Helper CD4 T Cells (T FH )
Crotty, S. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101400 · Cited by 2,738
Germinal Centers
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T follicular helper cell differentiation, function, and roles in disease
Crotty, S. (2014) · Immunity · doi:10.1016/j.immuni.2014.10.004 · Cited by 1,847
Foxp3+ follicular regulatory T cells control the germinal center response
Linterman, M. A., Pierson, W., Lee, S. K., Kallies, A., Kawamoto, S., Rayner, T. F., Srivastava, M., Divekar, D. P., Beaton, L., Hogan, J. J., et al. (2011) · Nature Medicine · doi:10.1038/nm.2425 · Cited by 1,292
Follicular helper T cells
Vinuesa, C. G., Linterman, M. A., Yu, D., & MacLennan, I. C. M. (2016) · Annual Review of Immunology · doi:10.1146/annurev-immunol-041015-055605 · Cited by 1,141

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Authors: Qi, H., Cannons, J. L., Klauschen, F., Schwartzberg, P. L., & Germain, R. N.
Affiliations: National Institutes of Health (US)
Corresponding author: Schwartzberg, Pamela L.
Germain, Ronald N.
ORCID: Qi, Hai
Cannons, Jennifer L.
Klauschen, Frederick
Schwartzberg, Pamela L.
Germain, Ronald N.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2008-10
Volume: 455
Issue: 7214
Pages: 764-769
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature07345
PMC: PMC2652134
OpenAlex: W1990297263
Cited by: 637
References: 45
Citations by year: 2026: 10 · 2025: 16 · 2024: 16 · 2023: 15 · 2022: 42 · 2021: 39 · 2020: 30 · 2019: 35 · 2018: 44 · 2017: 37 · 2016: 44 · 2015: 35 · 2014: 47 · 2013: 53 · 2012: 48
FWCI: 17.45
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: National Institutes of Health
National Institute of Allergy and Infectious Diseases (Z01AI000545)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: SH2D1A, X-linked lymphoproliferative disease, germinal center formation, T cell-B cell interaction, CD4+ T cell help, B cell activation, affinity maturation, intravital imaging
MeSH terms: Signaling Lymphocytic Activation Molecule Associated Protein, Animals, B-Lymphocytes, Cell Adhesion, Cell Communication, Cells, Cultured, Chimera, Dendritic Cells, Lymphocyte Activation, CD4-Positive T-Lymphocytes, Germinal Center, Intracellular Signaling Peptides and Proteins, Mice

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

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