| First Author | Qi H | Year | 2008 |
| Journal | Nature | Volume | 455 |
| Issue | 7214 | Pages | 764-9 |
| PubMed ID | 18843362 | Mgi Jnum | J:140086 |
| Mgi Id | MGI:3811926 | Doi | 10.1038/nature07345 |
| Citation | Qi H, et al. (2008) SAP-controlled T-B cell interactions underlie germinal centre formation. Nature 455(7214):764-9 |
| abstractText | 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. |
