Document Detail


Btk regulates multiple stages in the development and survival of B-1 cells.
MedLine Citation:
PMID:  17207856     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
B-1 cells are important players in the first line of defense against pathogens. According to current models for the origin of B-1 cells, they either represent a separate lineage from conventional B-2 cells or differentiate from conventional B-2 cells via an intermediate, B-1(int), in response to positive selection by antigen. Here we show that Btk, a Tec family kinase that mediates B cell antigen receptor (BCR) signaling, is required at multiple stages of B-1 cell development. VH12 anti-phosphatidylcholine (PtC) IgH transgenic mice provide a model for the induced differentiation of B-1 cells. This transgene selects for PtC-reactive cells and induces them to adopt a B-1 phenotype. Both processes have been shown to depend on Btk. To determine whether this is secondary to a requirement for Btk in the development of mature B-2 cells, we crossed VH12 transgenic mice to mice expressing low levels of Btk. B-2 cell development occurs normally in Btk(lo) mice despite reduced responsiveness to BCR crosslinking. Analysis of VH12.Btk(lo) mice reveals that Btk regulates the B-1(int) to B-1 transition and/or the survival of splenic B-1 cells, in part via a mechanism independent of its role in BCR signaling. We also show that Btk mediates the survival of, and expression of IL-10 by, those B-1 cells that do develop and migrate to the peritoneum. Multiple roles for Btk in B-1 cell development and maintenance may explain the particular sensitivity of this population to mutations in components of Btk signaling pathways.
Authors:
Cristina M Contreras; Kristina E Halcomb; Lindsey Randle; Rochelle M Hinman; Toni Gutierrez; Stephen H Clarke; Anne B Satterthwaite
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-01-04
Journal Detail:
Title:  Molecular immunology     Volume:  44     ISSN:  0161-5890     ISO Abbreviation:  Mol. Immunol.     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-02-19     Completed Date:  2007-06-01     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  7905289     Medline TA:  Mol Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  2719-28     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
B-Lymphocytes / cytology*,  enzymology,  immunology*
Cell Lineage* / genetics
Cell Survival
Mice
Mice, Inbred Strains
Mice, Transgenic
Peritoneum / immunology
Protein-Tyrosine Kinases / genetics,  physiology*
Receptors, Antigen, B-Cell / immunology
Receptors, IgE / immunology
Grant Support
ID/Acronym/Agency:
R01 AI 049248/AI/NIAID NIH HHS; R01 AI 29576/AI/NIAID NIH HHS; R01 AI 43587/AI/NIAID NIH HHS; R01 AI049248/AI/NIAID NIH HHS; T32 AI 005284-28/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Antigen, B-Cell; 0/Receptors, IgE; EC 2.7.10.1/Agammaglobulinaemia tyrosine kinase; EC 2.7.10.1/Protein-Tyrosine Kinases
Comments/Corrections

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