Human T-bet governs the generation of a distinct subset of CD11chighCD21low B cells.
Rui Yang, Danielle T Avery, Katherine J L Jackson, Masato Ogishi, Ibtihal Benhsaien, Likun Du, Xiaofei Ye, Jing Han, Jérémie Rosain, Jessica N Peel, Marie-Alexandra Alyanakian, Bénédicte Neven, Sarah Winter, Anne Puel, Bertrand Boisson, Kathryn J Payne, Melanie Wong, Amanda J Russell, Yoko Mizoguchi, Satoshi Okada, Gulbu Uzel, Christopher C Goodnow, Sylvain Latour, Jalila El Bakkouri, Aziz Bousfiha, Kahn Preece, Paul E Gray, Baerbel Keller, Klaus Warnatz, Stéphanie Boisson-Dupuis, Laurent Abel, Qiang Pan-Hammarström, Jacinta Bustamante, Cindy S Ma, Jean-Laurent Casanova, Stuart G Tangye
Science immunology 2022 Jul 22High-level expression of the transcription factor T-bet characterizes a phenotypically distinct murine B cell population known as "age-associated B cells" (ABCs). T-bet-deficient mice have reduced ABCs and impaired humoral immunity. We describe a patient with inherited T-bet deficiency and largely normal humoral immunity including intact somatic hypermutation, affinity maturation and memory B cell formation in vivo, and B cell differentiation into Ig-producing plasmablasts in vitro. Nevertheless, the patient exhibited skewed class switching to IgG1, IgG4, and IgE, along with reduced IgG2, both in vivo and in vitro. Moreover, T-bet was required for the in vivo and in vitro development of a distinct subset of human B cells characterized by reduced expression of CD21 and the concomitantly high expression of CD19, CD20, CD11c, FCRL5, and T-bet, a phenotype that shares many features with murine ABCs. Mechanistically, human T-bet governed CD21loCD11chi B cell differentiation by controlling the chromatin accessibility of lineage-defining genes in these cells: FAS, IL21R, SEC61B, DUSP4, DAPP1, SOX5, CD79B, and CXCR4. Thus, human T-bet is largely redundant for long-lived protective humoral immunity but is essential for the development of a distinct subset of human CD11chiCD21lo B cells.
Citation
Rui Yang, Danielle T Avery, Katherine J L Jackson, Masato Ogishi, Ibtihal Benhsaien, Likun Du, Xiaofei Ye, Jing Han, Jérémie Rosain, Jessica N Peel, Marie-Alexandra Alyanakian, Bénédicte Neven, Sarah Winter, Anne Puel, Bertrand Boisson, Kathryn J Payne, Melanie Wong, Amanda J Russell, Yoko Mizoguchi, Satoshi Okada, Gulbu Uzel, Christopher C Goodnow, Sylvain Latour, Jalila El Bakkouri, Aziz Bousfiha, Kahn Preece, Paul E Gray, Baerbel Keller, Klaus Warnatz, Stéphanie Boisson-Dupuis, Laurent Abel, Qiang Pan-Hammarström, Jacinta Bustamante, Cindy S Ma, Jean-Laurent Casanova, Stuart G Tangye. Human T-bet governs the generation of a distinct subset of CD11chighCD21low B cells. Science immunology. 2022 Jul 22;7(73):eabq3277
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PMID: 35867801
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