Publication Date:
2008-10-10
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652134/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652134/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Qi, Hai -- Cannons, Jennifer L -- Klauschen, Frederick -- Schwartzberg, Pamela L -- Germain, Ronald N -- Z01 AI000545-19/Intramural NIH HHS/ -- England -- Nature. 2008 Oct 9;455(7214):764-9. doi: 10.1038/nature07345.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lymphocyte Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18843362" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
B-Lymphocytes/*cytology/*immunology
;
CD4-Positive T-Lymphocytes/*cytology/*immunology
;
Cell Adhesion
;
Cell Communication
;
Cells, Cultured
;
Chimera/immunology
;
Dendritic Cells/immunology
;
Germinal Center/*cytology/*immunology
;
Intracellular Signaling Peptides and Proteins/deficiency/genetics/*metabolism
;
Lymphocyte Activation
;
Mice
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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