How specific is too specific? B-cell responses to viral infections reveal the importance of breadth over depth.
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.
Center for Comparative Medicine and the Department of Pathology, Microbiology & Immunology, University of California, Davis, Davis, CA 95616, USA. nbaumgarth@ucdavis.edu
Nicole
N
Baumgarth
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology; D009975:Orthomyxoviridae / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology* / Q000378:metabolism; D014780:Viruses / Q000276:immunology*
D007075:Immunoglobulin M
B-1 cells; antibody repertoire; antiviral immunity; extrafollicular foci; germinal centers; plasma cells