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Diet-induced obesity modifies B cell behavior, causing disruptions in humoral immunity 3387

Year: 2025
Type: article
Abstract: Description Obesity is a major public health concern in the USA, affecting over 100 million individuals and negatively impacting multiple organ systems. However, its effects on immune responses remain underexplored. In this study, we investigated how obesity alters B cell function and demonstrated that high-fat diet (HFD)-induced obesity disrupts B cell subset ratios compared to lean controls. Interestingly, obese mice developed spontaneous germinal centers but paradoxically showed reduced efficiency in responding to NP-CGG immunization and LCMV infection, indicating altered B cell development and differentiation. Adoptive transfer experiments revealed that these obesity-induced B cell dysregulations are cell intrinsic, persisting even after the transfer of B cells from obese donors to lean hosts. Further cellular and metabolic analyses we performed, highlighted comprehensive remodeling in B cells, including altered surface marker expression, a metabolic shift toward fat utilization, and modified leptin receptor signaling sensitivity. Single-cell RNA sequencing uncovered unique transcriptional profiles in B cells from obese mice both at rest and during infection. Using B cell-specific leptin receptor-deficient mice, we confirmed the critical role B cell leptin signaling plays in mediating obesity-driven changes. Collectively, these findings provide novel mechanistic insights into the impact of obesity on humoral immune responses. Funding Sources Start up funds from the Ohio State University College of Medicine Seed grant from OSU Infectious Disease Institute NIH / NIGMS R35 GM155038 Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)
DOI: 10.1093/jimmun/vkaf283.1198
Language: English
Subfield: Immunology
Open Access status: bronze
OpenAlex ID: W4416446295
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