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

Abstract:

: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-betlo MBCs and spleen-resident T-bethi 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.

journal_name

Immunity

journal_title

Immunity

authors

Johnson JL,Rosenthal RL,Knox JJ,Myles A,Naradikian MS,Madej J,Kostiv M,Rosenfeld AM,Meng W,Christensen SR,Hensley SE,Yewdell J,Canaday DH,Zhu J,McDermott AB,Dori Y,Itkin M,Wherry EJ,Pardi N,Weissman D,Naji A,Pra

doi

10.1016/j.immuni.2020.03.020

subject

Has Abstract

pub_date

2020-05-19 00:00:00

pages

842-855.e6

issue

5

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(20)30133-3

journal_volume

52

pub_type

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