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<p>Autoimmunity increases the risk of developing B lymphoma in humans; however, the molecular mechanism(s) underlying this link remain(s) unexplained. Here, we develop a mouse model to dissect the contribution of Id-driven T-B collaboration and show that chronic interaction between B cells and CD4<sup>+</sup> T cells first leads to autoimmunity and later to the development of B (and T) cell lymphomas. We find that serum autoantibodies and lymphoma B cell receptor (BCR) are related and have the same specificity for ubiquitous self-antigens (histone and nucleosome) (Signal 1). Self-reactive B lymphoma cells are helped by CD4<sup>+</sup> T cells that recognize a lymphoma neoantigen, an MHC class II-presented Idiotypic (Id) peptide (Signal 2). The mechanism, called Id-driven T-B collaboration, results in relentless mutual stimulation of B and T cells with germinal center markers, autoimmunity, and finally, malignant transformation of either B or T cells. Our results thus indicate Id-driven T-B collaboration as a potential mechanism linking autoimmunity and the development of lymphomas.</p>

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Idiotype-specific CD4+ T cells chronically stimulate autoreactive B cells to develop into B lymphomas in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月25日

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  • Ramakrishna Prabhu Gopalakrishnan,
  • Jerrold M. Ward,
  • Victor Greiff,
  • Ranveig Braathen,
  • Xian Hu,
  • Livia Bajelan,
  • Khang Lê Quý,
  • Ludvig Munthe,
  • Peter Csaba Huszthy,
  • Bjarne Bogen

摘要

Autoimmunity increases the risk of developing B lymphoma in humans; however, the molecular mechanism(s) underlying this link remain(s) unexplained. Here, we develop a mouse model to dissect the contribution of Id-driven T-B collaboration and show that chronic interaction between B cells and CD4+ T cells first leads to autoimmunity and later to the development of B (and T) cell lymphomas. We find that serum autoantibodies and lymphoma B cell receptor (BCR) are related and have the same specificity for ubiquitous self-antigens (histone and nucleosome) (Signal 1). Self-reactive B lymphoma cells are helped by CD4+ T cells that recognize a lymphoma neoantigen, an MHC class II-presented Idiotypic (Id) peptide (Signal 2). The mechanism, called Id-driven T-B collaboration, results in relentless mutual stimulation of B and T cells with germinal center markers, autoimmunity, and finally, malignant transformation of either B or T cells. Our results thus indicate Id-driven T-B collaboration as a potential mechanism linking autoimmunity and the development of lymphomas.