Heterosubtypic immunity to influenza A virus infection requires B cells but not CD8+ cytotoxic T lymphocytes

J Infect Dis. 2001 Feb 1;183(3):368-76. doi: 10.1086/318084. Epub 2000 Dec 20.


Heterosubtypic immunity (HSI), defined as protective cross-reactivity to lethal infection with influenza A virus of a serotype different from the virus initially encountered, is thought to be mediated by cross-reactive cytotoxic T lymphocytes (CTL). This study provides direct evidence for the role of effector CTL versus B cells in HSI in mice with a targeted disruption in the alpha chain of CD8 molecule (CD8(+) T cell deficient) or the immunoglobulin mu heavy chain (B cell deficient), respectively. CD8(+) T cell-deficient mice developed complete HSI. These mice displayed normal humoral immune responses, as determined by titers of subtype cross-reactive antibodies and virus-neutralizing antibodies specific for the immunizing influenza strain. In contrast, HSI was not observed in B cell-deficient mice, although these mice could mount cross-reactive CTL responses. These results show that B cells are required for HSI and provide new insight into the mechanisms of HSI, with significant implications in vaccine development.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • B-Lymphocytes / immunology*
  • CD8 Antigens / genetics
  • Cell Line
  • Cross Reactions
  • Cytokines / biosynthesis
  • Cytotoxicity Tests, Immunologic
  • Female
  • Gene Deletion
  • Genes, Immunoglobulin
  • Humans
  • Immunization
  • Immunoglobulin mu-Chains / genetics
  • Influenza A virus / immunology*
  • Influenza, Human / immunology*
  • Influenza, Human / mortality
  • Influenza, Human / virology
  • Lung / immunology
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured


  • Antibodies, Viral
  • CD8 Antigens
  • Cytokines
  • Immunoglobulin mu-Chains