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

By Hai Qi, Jennifer L Cannons, Frederick Klauschen, P. Schwartzberg, Ronald N. Germain. Nature, 2008

629 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/4f86fb6777d57ebfb32ee61d87c68e964cdbc7a4

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Citations in the corpus

• Follicular Helper T Cells. (2016, background): “Interactions between Tfh and B cells also maintain Tfh cells in the GC because SAP-deficient T cells, which cannot form stable interactions with B cells, are not retained in GCs (31).”
• FOLLICULAR HELPER T CELLS: LINEAGE AND LOCATION (2009, background): “The continued expression of OX40 on effector Tfh cells (Fazilleau et al., 2009; Qi et al., 2008) also suggests a role in the modulation of cell fate at effector Tfh cell-B cell interactions that may extend to within the GC reaction.”
• T follicular helper cell differentiation, function, and roles in disease (2014, background): “It appears that most cell types can be distinguished by differential expression of a set of 4–6 transcription factors (TFs) (Ravasi et al., 2010), and this concept applies to CD4 T cell differentiation (Ciofani et al.”
• From Vaccines to Memory and Back (2010, positive): “T FH cells produce IL-21 and their differentiation is dependent on Bcl-6 (Kassiotis and O’Garra, 2009) and a high avidity interaction with antigen specific B cells (Fazilleau et al., 2009; Qi et al., 2008).”