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. |