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Harnessing the duality of regulatory B cells: from identification of characteristic molecules to therapeutic
Luman Wang1,2, Ronghua Liu2,3, Yiwei Chu1,2
1Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
The field of immunology is increasingly intersecting with molecular biology, metabolic biology, and neurobiology (Zhu et al, A neuroimmune circuit mediates cancer cachexia-associated apathy. Science 2025;388:eadm8857; Jaschke et al, Gut-to-brain signaling restricts dietary protein intake during recovery from catabolic states. Cell 2025;188:7481-7494.e16; Zheremyan et al, Regulatory B cells: changing the landscape of immunoregulation and immunotherapy. Cytokine Growth Factor Rev 2025;86:121-36), marking a shift beyond traditional research approaches toward a more comprehensive understanding of the immune system. Central to this integrated perspective is the growing recognition that B cells are not only antibody producers, but also multifunctional cells dynamically modulated by their microenvironment. This comprehensive synthesis of recent research illuminates the dual nature of regulatory B cells (Bregs) as pivotal orchestrators of immune homeostasis. We examine how Bregs, governed by complex metabolic cues, neural signaling pathways, and local tissue microenvironments, can either suppress pathological inflammation or be co-opted to drive disease progression in autoimmunity, cancer, and allergic conditions. Understanding these microenvironmental determinants of Breg function is particularly critical for developing next-generation prognostic tools and targeted therapeutic strategies that effectively modulate B cell activity in various disease states.
The field of immunology is increasingly intersecting with molecular biology, metabolic biology, and neurobiology (Zhu et al, A neuroimmune circuit mediates cancer cachexia-associated apathy. Science 2025;388:eadm8857; Jaschke et al, Gut-to-brain signaling restricts dietary protein intake during recovery from catabolic states. Cell 2025;188:7481-7494.e16; Zheremyan et al, Regulatory B cells: changing the landscape of immunoregulation and immunotherapy. Cytokine Growth Factor Rev 2025;86:121-36), marking a shift beyond traditional research approaches toward a more comprehensive understanding of the immune system. Central to this integrated perspective is the growing recognition that B cells are not only antibody producers, but also multifunctional cells dynamically modulated by their microenvironment. This comprehensive synthesis of recent research illuminates the dual nature of regulatory B cells (Bregs) as pivotal orchestrators of immune homeostasis. We examine how Bregs, governed by complex metabolic cues, neural signaling pathways, and local tissue microenvironments, can either suppress pathological inflammation or be co-opted to drive disease progression in autoimmunity, cancer, and allergic conditions. Understanding these microenvironmental determinants of Breg function is particularly critical for developing next-generation prognostic tools and targeted therapeutic strategies that effectively modulate B cell activity in various disease states.
