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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
The link between antibodies to oxldl and natural protection against pneumococci depends on dh gene conservation
Journal of Experimental Medicine, Volume 210, No. 5, Year 2013
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Description
Selection and physiological production of protective natural antibodies (NAbs) have been associated with exposure to endogenous antigens. The extent to which this association depends on germline NAb sequence is uncertain. Here we show that alterations in germline DH sequence can sever the association between the production of self-reactive NAbs and NAbs that afford protection against a pathogen. In unmanipulated hosts, the availability of the evolutionarily conserved DFL16.1 gene segment sequence profoundly affected the serum levels of NAbs against bacterial phosphorylcholine but not oxidized low-density lipoprotein. Mice with partially altered DFL16.1 sequence could use N nucleotides to recreate the amino acid sequence associated with the classical protective T15 idiotype-positive NAbs, whereas those without DFL16.1 could not. DFL16.1 gene-deficient mice proved more susceptible to challenge with live Streptococcus pneumoniae. Our findings indicate that although production of self-reactive NAbs can be independent of germline DH sequence, their capacity to provide protection against pathogens cannot. The potential relevance of these findings for the rational design of vaccines is discussed. ©2013 Vale et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3646500/bin/supp_210_5_875__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3646500/bin/supp_jem.20121861_JEM_20121861_sm.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3646500/bin/supp_jem.20121861_JEM_20121861_TableS1.xlsx
Authors & Co-Authors
Vale, André Macedo
United States, Birmingham
Department of Genetics
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Kapoor, Pratibha
United States, Birmingham
Department of Genetics
Skibinski, Greg A.
United States, Birmingham
Department of Genetics
Elgavish, Ada
United States, Birmingham
Department of Genetics
Mahmoud, Tamer I.
United States, Birmingham
Department of Genetics
Egypt, Cairo
Faculty of Pharmacy
Zemlin, Cosima
United States, Birmingham
Department of Genetics
Zemlin, Michael
United States, Birmingham
Department of Genetics
Germany, Marburg
Philipps-universität Marburg
Burrows, Peter Daniel
United States, Birmingham
Department of Genetics
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Nobrega, Alberto
Brazil, Rio de Janeiro
Universidade Federal do Rio de Janeiro
Kearney, John F.
United States, Birmingham
Department of Genetics
Briles, David E.
United States, Birmingham
Department of Genetics
Schroeder, Harry W.
United States, Birmingham
Department of Genetics
Statistics
Citations: 12
Authors: 12
Affiliations: 4
Identifiers
Doi:
10.1084/jem.20121861
ISSN:
00221007
e-ISSN:
15409538
Research Areas
Genetics And Genomics