Document Detail


Critical role of SAP in progression and reactivation but not maintenance of T cell-dependent humoral immunity.
MedLine Citation:
PMID:  23319045     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is a small adaptor molecule mutated in X-linked lymphoproliferative disease, a human immunodeficiency. SAP plays a critical role in the initiation of T cell-dependent B cell responses leading to germinal center reaction, the production of high-affinity antibodies, and B cell memory. However, whether SAP has a role in these responses beyond their initiation is not known. It is important to address this matter 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 inducibly SAP deficient mouse, we found that SAP was required not only for the initiation but also for the progression of primary T cell-driven B cell responses to haptens. It was also necessary for the reactivation of T cell-dependent B cell immunity during secondary immune responses. These activities consistently correlated with the requirement of SAP for full expression of the 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 for maintenance, of T cell-driven B cell humoral immunity. These findings may have implications for the treatment of immune disorders by targeting the SAP pathway.
Authors:
Ming-Chao Zhong; André Veillette
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-14
Journal Detail:
Title:  Molecular and cellular biology     Volume:  33     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-22     Completed Date:  2013-07-05     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1223-32     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular Oncology, Clinical Research Institute of Montreal, Montreal, Quebec, Canada. zhongmc@ircm.qc.ca
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibody-Producing Cells / immunology,  metabolism
B-Lymphocytes / immunology,  metabolism
Haptens / immunology,  metabolism
Immunity, Humoral / immunology
Immunologic Memory / immunology
Intracellular Signaling Peptides and Proteins / immunology*,  metabolism
Lymphocyte Activation / immunology
Male
Mice
Mice, Inbred C57BL
Proto-Oncogene Proteins c-bcl-6 / immunology,  metabolism
T-Lymphocytes / immunology*,  metabolism
Grant Support
ID/Acronym/Agency:
//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Haptens; 0/Intracellular Signaling Peptides and Proteins; 0/Proto-Oncogene Proteins c-bcl-6; 0/Sh2d1a protein, mouse
Comments/Corrections

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