| Critical role of SAP in progression and re-activation, but not maintenance, of T cell-dependent humoral immunity. | |
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MedLine Citation:
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PMID: 23319045 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is a small adaptor molecule mutated in X-linked lymphoproliferative disease, a human immunodeficiency. It plays a critical role in initiation of T cell-dependent B cell responses leading to germinal center reaction, production of high affinity antibodies and B cell memory. However, whether SAP has a role in these responses beyond their initiation is not known. This matter is important to address not only for mechanistic reasons, but also because blockade of the SAP pathway is being contemplated as a means to treat autoimmune diseases in humans. Using an inducible SAP-deficient mouse, we found that SAP was required not only for initiation, but also for progression of primary T cell-driven B cell responses to haptens. It was also necessary for re-activation of T cell-dependent B cell immunity during secondary immune responses. These activities consistently correlated with the requirement of SAP for full expression of lineage commitment factor, Bcl-6, in follicular T helper (T(FH)) cells. However, once memory B cells and long-lived antibody-secreting cells were established, SAP became dispensable for maintaining T cell-dependent B cell responses. Thus, SAP is pivotal for nearly all phases, but not maintenance, of T cell-driven B cell humoral immunity. These findings may have implications for treating immune disorders by targeting the SAP pathway. |
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Authors:
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Ming-Chao Zhong; André Veillette |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-14 |
Journal Detail:
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Title: Molecular and cellular biology Volume: - ISSN: 1098-5549 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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From the Laboratory of Molecular Oncology, Clinical Research Institute of Montréal, Montréal, Québec, Canada H2W 1R7. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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