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B cells: Your besT-bet against the flu

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Science Immunology  05 Jun 2020:
Vol. 5, Issue 48, eabd0542
DOI: 10.1126/sciimmunol.abd0542

Abstract

T-bet+ memory B cells are a distinct subset that home to the spleen and produce neutralizing antibodies against influenza.

T-bet is a transcription factor that has traditionally been associated with T cells activated by intracellular pathogens including viruses. However, recent literature has shown that a subset of B cells can express T-bet during chronic infection and autoimmune states. Johnson et al. further our understanding of T-bet+ B cells in immunity by using a Tbet reporter mouse line and tracking antigen-specific B cells after influenza infection. Influenza-specific B cells were found to inhabit different niches based on their level of T-bet expression. Despite detection in the lungs, mediastinal lymph nodes, and peripheral blood during acute infection, by day 40, T-bethi antigen-specific B cells were only found in the spleen. This splenic localization was confirmed via a parabiosis model, where previously infected mice were surgically joined to naive congenic partners. Although antigen-specific memory B cells were seen in both mice, the T-bethi subset remained resident in the spleen of antigen-experienced mice. Similar results were observed in samples from humans, with almost no T-bet+ B cells found in lymph nodes, although a direct comparison of differing T-bet levels between reporters in mice and staining in human B cells is difficult given differences in method detection. Spleen residency of T-bet+ memory B cells is an important new finding, the role of which remains to be determined. It raises some new questions, including how or even whether this memory population is reactivated by a virus that is presumably delimited to the lung during reexposure. B cell lineage analysis of Tbet+ versus Tbet B cells suggested that they are interchangeable before memory formation, but then diverge to stably commit into segregated populations. Further, B cell–specific loss of T-bet resulted in impaired IgG2c antibody responses to influenza antigenic targets, including ones known to be relevant for broadly neutralizing antibodies. This underscores the importance of T-bet in memory B cells during viral infection. It will be important in future work to clarify how this new understanding of T-bet–expressing memory B cells is relevant to other immune states such as autoimmunity and infectious states induced by pathogens other than viruses.

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