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Cholinergic B cells: New players in immune regulation and tissue homeostasis

Cellular & Molecular Immunology volume 22, pages 696–698 (2025)Cite this article

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As key players in humoral immunity, B cells play diverse roles in immune responses and disease development. Although early studies focused on the hallmark features of antibody production in B cells, increasing evidence has demonstrated the effector functions of cytokine secretion and antigen presentation by B cells in the development of various human diseases. Recent studies on the interactions of immune cells and nerve systems through neurotransmitters, including acetylcholine (ACh), have revealed novel functions of B cells in immune regulation and tissue homeostasis. Two newly published studies in Nature Immunology and Immunity demonstrated that B cells produce ACh to modulate antiviral inflammatory responses and liver regeneration after injury [1, 2]. These pivotal findings suggest the existence of a new functional subset of ACh-producing B cells, termed “cholinergic B cells”, which are characterized by their ability to synthesize ACh via high expression of choline acetyltransferase (ChAT). Cholinergic B cells span both innate B1 and conventional B2 cells and play a unique role in bridging neuroimmune crosstalk. Thus, elucidation of the functional features of cholinergic B cells will open new avenues for therapeutic intervention in acute inflammatory and regenerative disorders.

It has been reported that vagus nerve-derived ACh suppresses proinflammatory cytokine production by macrophages through a cholinergic anti-inflammatory pathway [3]. Moreover, immune cells, including B cells, produce massive amounts of ACh upon inflammation induction, suggesting neuron-independent production of ACh. ChAT+ cholinergic B cells have been shown to regulate local innate but not adaptive immunity in an adoptive transfer model of colitis [4]. Notably, B cells are important sources of ACh in the bone marrow, and cholinergic B cells limit steady-state and emergency hematopoiesis by regulating α7-nicotinic-ACh receptor (α7nAChR)+ bone marrow stromal cells [5]. The available evidence also shows that B-cell-derived ACh suppresses acute and chronic cardiovascular inflammation and disease severity by regulating immune cell responses [5]. These findings provide a solid rationale for in-depth investigations on how cholinergic B cells affect pathophysiological processes across diverse organs and tissues. Here, the findings from two newly published papers support the notion that cholinergic B cells are a distinct subset with immunomodulatory functions in viral infections and tissue regeneration.

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Acknowledgements

Dr. Liwei Lu dedicates this work to Dr. Dennis G. Osmond at McGill University for his pioneering research in B-cell immunology. This work was supported by the National Natural Science Foundation of China (82471821), the Hong Kong Research Grants Council (17116424, 17111222, 17103821), and the Centre for Oncology and Immunology under the Health@InnoHK Initiative funded by the Innovation and Technology Commission, Hong Kong, China. The figure was created with BioRender.com with the permission of the publication license.

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Authors and Affiliations

  1. Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, China

    Fan Xiao, Lam Ng, Chong Deng & Liwei Lu

  2. Centre for Infection and Immunity Studies, School of Medicine, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China

    Kongyang Ma

  3. Centre for Oncology and Immunology, Hong Kong Science Park, Hong Kong, China

    Chong Deng & Liwei Lu

  4. Department of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China

    Xiaoxia Zhu & Hejian Zou

  5. Department of Dermatology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, 410011, China

    Haijing Wu

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  1. Fan Xiao
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Correspondence to Haijing Wu or Liwei Lu.

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The authors declare that they have no conflicts of interest. Dr. Liwei Lu is an editorial board member of Cellular & Molecular Immunology, but he has not been involved in peer review or decision-making related to the article.

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Xiao, F., Ng, L., Ma, K. et al. Cholinergic B cells: New players in immune regulation and tissue homeostasis. Cell Mol Immunol 22, 696–698 (2025). https://doi.org/10.1038/s41423-025-01300-y

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