Document Detail


B cell receptor signal transduction in the GC is short-circuited by high phosphatase activity.
MedLine Citation:
PMID:  22555432     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Germinal centers (GCs) generate memory B and plasma cells, which are essential for long-lived humoral immunity. GC B cells with high-affinity B cell receptors (BCRs) are selectively expanded. To enable this selection, BCRs of such cells are thought to signal differently from those with lower affinity. We show that, surprisingly, most proliferating GC B cells did not demonstrate active BCR signaling. Rather, spontaneous and induced signaling was limited by increased phosphatase activity. Accordingly, both SH2 domain-containing phosphatase-1 (SHP-1) and SH2 domain-containing inositol 5 phosphatase were hyperphosphorylated in GC cells and remained colocalized with BCRs after ligation. Furthermore, SHP-1 was required for GC maintenance. Intriguingly, GC B cells in the cell-cycle G(2) period regained responsiveness to BCR stimulation. These data have implications for how higher-affinity B cells are selected in the GC.
Authors:
Ashraf M Khalil; John C Cambier; Mark J Shlomchik
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-05-03
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  336     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-01     Completed Date:  2012-09-14     Revised Date:  2013-09-24    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1178-81     Citation Subset:  IM    
Affiliation:
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibody Affinity
Antigen Presentation
Antigens / immunology
Antigens, CD79 / metabolism
B-Lymphocytes / enzymology,  immunology*,  metabolism
Calcium / metabolism
Cell Cycle
Down-Regulation
Germinal Center / cytology,  immunology*
Intracellular Signaling Peptides and Proteins / metabolism
Lymphocyte Activation
Mice
Mice, Inbred BALB C
Mice, Transgenic
Models, Immunological
Phosphoric Monoester Hydrolases / metabolism
Phosphorylation
Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism*
Protein-Tyrosine Kinases / metabolism
Receptors, Antigen, B-Cell / immunology*,  metabolism*
Signal Transduction
Grant Support
ID/Acronym/Agency:
AI43603/AI/NIAID NIH HHS; AR44077/AR/NIAMS NIH HHS; R01 AI043603/AI/NIAID NIH HHS; R01 AR044077/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Antigens; 0/Antigens, CD79; 0/Intracellular Signaling Peptides and Proteins; 0/Receptors, Antigen, B-Cell; 7440-70-2/Calcium; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.1/Syk kinase; EC 3.1.3.-/Phosphoric Monoester Hydrolases; EC 3.1.3.48/Protein Tyrosine Phosphatase, Non-Receptor Type 6; EC 3.1.3.48/Ptpn6 protein, mouse; EC 3.1.3.56/inositol-1,4,5-trisphosphate 5-phosphatase
Comments/Corrections
Comment In:
Nat Rev Immunol. 2012 Jun;12(6):398-9   [PMID:  22596411 ]
Science. 2012 Jun 1;336(6085):1120-1   [PMID:  22654048 ]

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