Obesity suppresses B cell development and impairs antibody production upon antigen challenge

Obesity promotes a diminished response to vaccinations and infections. Therefore, understanding how obesity targets B cell‐driven humoral immunity, particularly at a mechanistic level, is essential to elucidate. Using a murine model, we report that diet‐induced obesity impairs early B cell development and induces a dysfunctional immune response. B cells from obese mice displayed a two‐fold reduction in the number of CD19 + cells, resulting in decreased frequencies of various B cell subsets in the bone marrow. Early lymphoid commitment markers such as IL7Rα, IL7R, and STAT5 showed significantly decreased expression at the transcript level. In addition, obese mice had reduced mRNA expression of the B cell lymphopoiesis markers, PAX5 and Oct2, compared to controls. Functionally, B cells from obese mice had elevated IgM and IgG levels in the absence of stimulation. When B cells from the obese mice were challenged with anti‐TLR4 or anti‐BCR/TLR9 in vitro, the ability to produce IgM and IgG was diminished. Overall, these findings demonstrate that obesity hinders B cell development and drives a dysregulated immune response, which could contribute to impaired responses to infections and vaccinations. Support or Funding Information Supported by NIH R01AT008375 (SRS)