Abstract

Obesity-a major risk factor for multiple disorders, including cardiovascular disease and cancer-has tripled globally in less than 50 years and is associated with a chronic inflammatory response. B cells play a central role in driving obesity-associated meta-inflammation, and here we provide a consolidated summary of human B cell dysregulation and the molecular switches potentially driving this B cell dysregulation. A new frontier within the obesity research field, highlighted by the COVID-19 pandemic, is that obesity impacts the ability to respond to and clear infections and we propose a model by which obesity establishes a new "set-point" in the B cell compartment which contributes to this. Obesity increases the risk of type 2 diabetes mellitus, cardiovascular disease, fatty liver disease, and cancer. It is also linked with more severe complications from infections, including COVID-19, and poor vaccine responses. Chronic, low-grade inflammation and associated immune perturbations play an important role in determining morbidity in people living with obesity. The contribution of B cells to immune dysregulation and meta-inflammation associated with obesity has been documented by studies over the past decade. With a focus on human studies, here we consolidate the observations demonstrating that there is altered B cell subset composition, differentiation, and function both systemically and in the adipose tissue of individuals living with obesity. Finally, we discuss the potential factors that drive B cell dysfunction in obesity and propose a model by which altered B cell subset composition in obesity underlies dysfunctional B cell responses to novel pathogens.