Dysfunction in neuro-mesenchymal units impairs the development of bone marrow B cells in mice with anxiety.

• The neuro-mesenchymal units regulate bone marrow B cell development mainly via the norepinephrine-Cxcl12 pathway. • Targeting these neuro-mesenchymal units not only restored B cell development but also alleviated anxiety-like behavior in the mice. • Anxiety disorders can create a vicious cycle, perpetuating ongoing mental and immunological damage and ultimately leading to irreversible harm. The reduction in B lymphocytes observed in individuals with anxiety disorders may compromise antiviral responses, yet the precise mechanisms behind this decline remain unclear. While elevated glucocorticoid levels have been suggested as contributing factors, anxiety disorders are associated with diminished glucocorticoid signaling. Given that autonomic nervous system dysfunction is a hallmark of anxiety disorders, we established an anxiety-related behavior mouse model by stimulating C1 neurons in the rostral ventrolateral medulla. Using this model, we confirmed that sustained activation of sympathetic nerves can disrupt adaptive immunity, particularly affecting the development of B cells. The underlying mechanism involves the control of B cell development through neuro-mesenchymal units within the bone marrow, with mesenchyme-derived CXCL12 playing a pivotal role in this regulatory process. Intriguingly, targeting these neuro-mesenchymal units not only restored B cell development but also alleviated anxiety-like behavior in the mice. Our study provides compelling evidence regarding the regulatory role of neuro-mesenchymal units in the development of B cells within the bone marrow. Additionally, our findings suggest that anxiety disorders can create a vicious cycle, perpetuating ongoing mental and immunological damage and ultimately leading to irreversible harm. To break this cycle, it is essential to focus on the dysfunction of immune cells and strive to restore immune homeostasis in individuals suffering from anxiety disorders. [ABSTRACT FROM AUTHOR]