The Transcription Factor T-bet Resolves Memory B Cell Subsets with Distinct Tissue Distributions and Antibody
John L Johnson1, Rebecca L Rosenthal1, James J Knox1
1Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Immunity
|May 1, 2020
Summary
Transcription factor T-bet defines distinct memory B cell subsets crucial for influenza immunity. These T-bet+ and T-bet- cells exhibit unique tissue residency and antibody production, impacting humoral immune memory.
Area of Science:
- Immunology
- Cell Biology
- Virology
Background:
- B cells expressing T-bet are linked to immune responses and autoimmunity.
- Understanding memory B cell (MBC) subsets is vital for vaccine development and autoimmune disease research.
Purpose of the Study:
- To investigate the distribution, relationships, and functions of T-bet-expressing (T-bet+) and T-bet-negative (T-bet-) memory B cells.
- To elucidate the role of T-bet+ MBCs in the influenza-specific immune response.
Main Methods:
- Lineage tracing and immunoglobulin heavy chain (IgH) repertoire analysis in mice.
- Parabiosis experiments to study tissue residency and recirculation.
- Conditional gene deletion to assess T-bet function in B cells.
Main Results:
- Both T-bet+ and T-bet- HA-specific B cells develop into long-lived MBCs with minimal interconversion.
- T-bet+ MBCs show distinct subtypes (T-betlo recirculating and T-bethi spleen-resident) with differential tissue homing.
- T-bet is essential for producing HA stalk-specific IgG2c antibodies and maintaining durable neutralizing immunity to influenza.
Conclusions:
- T-bet expression delineates functionally distinct MBC subsets with unique homing and residency properties.
- These T-bet-defined MBC subsets mediate different aspects of humoral immune memory against influenza.
- Findings highlight T-bet as a key regulator of adaptive humoral immunity.
Keywords:
Age-associated B cellsB cell memoryBCR sequencingHumoral immunityT-bet(+) B cellsantibodyhemagglutinin stalkimmune repertoire profilinginfluenzatissue-residentMore Related Videos
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