Authors: 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
Published: 2022-07-22
DOI: 10.1126/sciimmunol.abq3277
Source: Full article
High-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 CD21