Document Detail


Molecular characterization of the cervical and systemic B-cell repertoire: Unique, yet overlapping, immune compartments of an HIV-1 resistant individual.
MedLine Citation:
PMID:  21293180     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cervical mucosa of women who are highly exposed to HIV-1, yet remain persistently seronegative (HEPS), presents a unique opportunity to study the dynamics of an immune compartment potentially capable of preventing HIV-1 infection. Herein, we provide a detailed characterization of the immunoglobulin repertoire of cervical and systemic B cells from one such HEPS individual from Nairobi, Kenya. Analysis was done on 512 VH sequences that were RT-PCR amplified from B cells in a paired sample from the cervix and peripheral blood. The VH3 and DH repertoire of class switched cervical B cells differs significantly from that of systemic B cells indicating that the cervical environment affects local B cell populations and hence VH gene expression. Six networks of clonally related, heavily mutated B cells were identified that spanned the systemic and cervical B cell compartments. Analysis of somatic mutations suggests this is likely the result of systemic, class switched B cells homing to the cervical mucosa. Multiple networks of somatically mutated V-gene sequences, unique to the cervical mucosa, were also identified. This supports the notion that site specific responses occur and have unique regulation of tolerance and recruitment into local memory or blast B cell compartments. We conclude that while the nature of the cervical environment shapes the local B cell repertoire, the infusion of post germinal center B cells to the human cervix is a common occurrence, and represents a means by which systemic immunization could provide the local antibodies necessary to prevent HIV-1 at the site of initial contact.
Authors:
Ryan G Gaudet; Felix Breden; Frank Plummer; Jody D Berry
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-03-01
Journal Detail:
Title:  mAbs     Volume:  3     ISSN:  1942-0870     ISO Abbreviation:  MAbs     Publication Date:    2011 Mar-Apr
Date Detail:
Created Date:  2011-04-05     Completed Date:  2011-08-15     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  101479829     Medline TA:  MAbs     Country:  United States    
Other Details:
Languages:  eng     Pagination:  181-91     Citation Subset:  IM    
Affiliation:
Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.
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MeSH Terms
Descriptor/Qualifier:
B-Lymphocyte Subsets / immunology*
B-Lymphocytes / immunology*
Base Sequence
Cervix Uteri / immunology*
Cloning, Molecular
Female
Genes, Immunoglobulin / genetics*
HIV Infections / immunology,  prevention & control*
HIV Seronegativity / immunology*
HIV-1 / immunology*
Humans
Immunoglobulin Heavy Chains / genetics
Immunoglobulin Variable Region
Immunologic Memory / immunology
Kenya
Molecular Sequence Data
Mutation
Sequence Analysis, DNA
Grant Support
ID/Acronym/Agency:
//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Immunoglobulin Heavy Chains; 0/Immunoglobulin Variable Region
Comments/Corrections

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