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Publication : The Transcription Factor T-bet Resolves Memory B Cell Subsets with Distinct Tissue Distributions and Antibody Specificities in Mice and Humans.

First Author  Johnson JL Year  2020
Journal  Immunity Volume  52
Issue  5 Pages  842-855.e6
PubMed ID  32353250 Mgi Jnum  J:288602
Mgi Id  MGI:6432001 Doi  10.1016/j.immuni.2020.03.020
Citation  Johnson JL, et al. (2020) The Transcription Factor T-bet Resolves Memory B Cell Subsets with Distinct Tissue Distributions and Antibody Specificities in Mice and Humans. Immunity 52(5):842-855.e6
abstractText  B cell subsets expressing the transcription factor T-bet are associated with humoral immune responses and autoimmunity. Here, we examined the anatomic distribution, clonal relationships, and functional properties of T-bet(+) and T-bet(-) memory B cells (MBCs) in the context of the influenza-specific immune response. In mice, both T-bet(-) and T-bet(+) hemagglutinin (HA)-specific B cells arose in germinal centers, acquired memory B cell markers, and persisted indefinitely. Lineage tracing and IgH repertoire analyses revealed minimal interconversion between T-bet(-) and T-bet(+) MBCs, and parabionts showed differential tissue residency and recirculation properties. T-bet(+) MBCs could be subdivided into recirculating T-bet(lo) MBCs and spleen-resident T-bet(hi) MBCs. Human MBCs displayed similar features. Conditional gene deletion studies revealed that T-bet expression in B cells was required for nearly all HA stalk-specific IgG2c antibodies and for durable neutralizing titers to influenza. Thus, T-bet expression distinguishes MBC subsets that have profoundly different homing, residency, and functional properties, and mediate distinct aspects of humoral immune memory.
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