Sequential Evolution of B Cell Memory

RESEARCH HIGHLIGHTS

Nature Reviews Immunology | Published online 25 January 2016; doi:10.1038/nri.2016.15

of the IgG1+ memory B cell popu- lation had formed by day 5, before the germinal centre response. Peak formation of IgG1+ memory B cells occurred between days 6 and 8, and these cells were of germinal centre origin. By contrast, the majority of long-lived plasma cells started to emerge after the peak of the germinal centre response at day 14 post- immunization, and substantial plasma cell generation continued up to and beyond week 5. These IMMUNE MEMORY observations were validated in three additional systems: in wild-type mice

S. Bradbrook/NPG during a polyclonal response; by disrupting the peak germinal centre Sequential evolution of response and assessing the change in plasma cell output; and through B cell memory variable region gene sequencing. Three functionally distinct subsets of memory B cells (distinguished There has been much debate unclear. In addition, the signals that by CD80 and PDL2 expression) on the development of memory control the differentiation of germinal have been described, and this study B cells and long-lived plasma cells centre B cells into memory B cells also showed that the heterogeneity during a germinal centre response. versus long-lived plasma cells remain within the memory B cell pool is Understanding how these cells are controversial. reflected in their temporal generation. generated has important implica- In an effort to resolve these issues, Furthermore, the authors showed that tions for vaccine design, as well Weisel et al. developed a system that early and late germinal centre B cells as for our understanding of auto allowed them to label long-lived had unique transcriptional profiles. immunity and pathogen persistence. B cells specifically at the time point Further analysis of these data should Reporting in Immunity, Shlomchik of their generation during a syn- help to identify key signals that deter- and colleagues now show that the chronized germinal centre response. mine the temporal evolution of B cells maturation of the germinal centre Following antigen immunization, during the germinal centre response. response promotes the sequential bromodeoxyuridine (BrdU) was So, this study shows that a pro- formation of memory B cell subsets administered to groups of mice over portion of long-lived memory B cells and long-lived plasma cells. consecutive 3-day periods (termed are made before the germinal centre The development of a memory labelling windows) and, at 8 weeks response and that the germinal centre B cell response to a T cell-dependent important post-immunization, the percentage undergoes a temporal switch for the + antigen first involves the generation implications for of BrdU memory B cells or long- sequential generation of memory of short-lived plasmablasts and is lived plasma cells from a particular B cells and long-lived plasma cells. vaccine design, followed by the germinal centre labelling window was analysed. Olive Leavy response, which produces both as well as for our This analysis of the kinetics of ORIGINAL ARTICLE Weisel, F. J. et al. A temporal memory B cells and long-lived understanding long-lived B cell memory formation switch in the germinal center determines differential output of memory B and plasma cells. plasma cells. Before germinal centre of autoimmunity showed that there was a pronounced formation, antigen-experienced wave of IgM+ B cell formation Immunity http://dx.doi.org/10.1016/ and pathogen j.immuni.2015.12.004 (2016) memory-like B cells are also present, before the start of the germinal FURTHER READING De Silva, N. S. & Klein, U. but whether these cells contribute persistence centre response (days 3–4 post- Dynamics of B cells in germinal centres. Nat. Rev. Immunol. 15, 137–148 (2015) to the long-lived memory pool is immunization). In addition, ~9%

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