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Changes in the mature antibody repertoire may impair heterosubtypic immunity to influenza A virus infection in the aged
Author(s) -
Schroeder H,
Buckley K,
Nguyen H,
Schelonka R,
Zhuang Y,
Wang D,
Brown M,
Mestecky J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.847.17
Subject(s) - repertoire , biology , virus , dominance (genetics) , antibody , influenza a virus , immunosenescence , immunology , immunity , virology , immune system , genetics , gene , physics , acoustics
ΔD‐iD mice express a CDR‐H3 repertoire enriched for charged amino acids. After a heterosubtypic challenge with influenza A virus, young homozygous ΔD‐iD suffer increased morbidity and mortality. To test dominance, we challenged ten heterozygous ΔD‐iD, ten homozygous ΔD‐DFL, and ten wild‐type mice. All of the ΔD‐DFL and wild‐type mice survived, whereas eight heterozygous ΔD‐iD mice died (p<0.001). Aged individuals are particularly susceptible to influenza. We evaluated CDR‐H3 repertoire development in the bone marrow of 26mo old mice. We found that developing B cells from these aged mice failed to demonstrate the progressive enrichment for tyrosine seen in the young. Instead, almost 10% of sequences from the mature, recirculating fraction of B cells in the aged mice retained an average hydrophobicity ≤‐0.68 (p<0.05). These findings suggest a possible relationship between failure to properly regulate the CDR‐H3 repertoire and immunosenescence.