1. Higher levels of B-cell mutation in the early germinal centres of an inefficient secondary antibody response to a variant influenza haemagglutinin.
- Author
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Tennant RK, Holzer B, Love J, Tchilian E, and White HN
- Subjects
- Animals, Antibody Affinity, Cross Reactions, Female, Hemagglutinins, Viral genetics, Hemagglutinins, Viral metabolism, Humans, Immunity, Humoral, Immunization, Secondary, Immunologic Memory, Mice, Mice, Inbred BALB C, Mutation genetics, Polymorphism, Genetic, B-Lymphocytes physiology, Germinal Center immunology, Influenza Vaccines immunology, Influenza, Human immunology, Receptors, Antigen, B-Cell genetics
- Abstract
Designing improved vaccines against mutable viruses such as dengue and influenza would be helped by a better understanding of how the B-cell memory compartment responds to variant antigens. Towards this we have recently shown, after secondary immunization of mice with a widely variant dengue virus envelope protein with only 63% amino acid identity, that IgM
+ memory B cells with few mutations supported an efficient secondary germinal centre (GC) and serum response, superior to a primary response to the same protein. Here, further investigation of memory responses to variant proteins, using more closely related influenza virus haemagglutinins (HA) that were 82% identical, produced a variant-induced boost response in the GC dominated by highly mutated B cells that failed, not efficiently improving serum avidity even in the presence of extra adjuvant, and that was worse than a primary response. This supports a hypothesis that over a certain level of antigenic differences, cross-reactive memory B-cell populations have reduced competency for affinity maturation. Combined with our previous observations, these findings also provide new parameters of success and failure in antibody memory responses., (© 2019 The Authors. Immunology Published by John Wiley & Sons Ltd.)- Published
- 2019
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