How specific is too specific? B-cell responses to viral infections reveal the importance of breadth over depth

Immunol Rev. 2013 Sep;255(1):82-94. doi: 10.1111/imr.12094.


Influenza virus infection induces robust and highly protective B-cell responses. Knowledge gained from the analysis of such protective humoral responses can provide important clues for the design of successful vaccines and vaccination approaches and also provides a window into the regulation of fundamental aspects of B-cell responses that may not be at play when responses to non-replicating agents are studied. Here, I review features of the B-cell response to viruses, with emphasis on influenza virus infection, a highly localized infection of respiratory tract epithelial cells, and a response that is directed against a virus that continuously undergoes genetic changes to its surface spike protein, a major target of neutralizing antibodies. Two aspects of the B-cell response to influenza are discussed here, namely polyreactive natural antibodies and the role and function of germinal center responses. Both these features of the B-cell response raise the question of how important antibody fine-specificity is for long-term protection from infection. As outlined, the pathogenesis of influenza virus and the nature of the antiviral B-cell response seem to emphasize repertoire diversity over affinity maturation as driving forces behind the influenza-specific B-cell immunity.

Keywords: B-1 cells; antibody repertoire; antiviral immunity; extrafollicular foci; germinal centers; plasma cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • Humans
  • Immunoglobulin M / immunology
  • Influenza, Human / immunology
  • Orthomyxoviridae / immunology
  • Orthomyxoviridae Infections / immunology
  • T-Lymphocyte Subsets / immunology
  • Virus Diseases / immunology*
  • Virus Diseases / metabolism
  • Viruses / immunology*


  • Immunoglobulin M