Authors
Ana Maria Hincapie, Alexandre Poirier, Isabelle Aubry, Philippe Aumont, Aanya Bhagrath, Noriko Uetani, Bianca Colalillo, Chenyue Wu, Benoit Charbonneau, Stephanie Bussieres-Marmen, Belma M Abidin, Javier M Di Noia, Judith N Mandl, Silvia M Vidal, Jorg H Fritz, Michel L Tremblay
Published in
Science advances. Volume 12. Issue 34. Pages eaec0162. Aug 21, 2026. Epub Aug 19, 2026.
Abstract
Antigen-specific humoral responses are critical for long-term protection against infectious diseases, yet the mechanisms that regulate B cell differentiation and antibody production remain incompletely defined. Here, we identify the Protein Tyrosine Phosphatase Nonreceptor Type 2 (Ptpn2) as a B cell-intrinsic regulator of plasma cell fate and isotype switching. Using a B cell-specific Ptpn2 knockout mouse model, we show that Ptpn2 restrains both B cell receptor and interferon-γ (IFN-γ) signaling by directly dephosphorylating Lyn, STAT1, and STAT3. Loss of Ptpn2 leads to hyperactivation of these two signaling pathways, resulting in transcriptional reprogramming that promotes plasma cell differentiation and increased IFN-γ-driven antibody production. Functionally, Ptpn2-deficient mice generated enhanced primary antiviral antibody responses following influenza infection and elevated virus-specific and neutralizing titers upon recall without compromising affinity. These findings identify Ptpn2 as a key intracellular checkpoint that integrates antigenic and inflammatory cues to regulate humoral immunity, with potential implications for enhancing vaccine-induced protective immunity.
PMID:
42616863
Bibliographic data and abstract were imported from PubMed on 20 Aug 2026.
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