Assistant Professor The University of Texas at San Antonio San Antonio, Texas, United States
Disclosure(s):
Benjamin T. Enslow, MD: No financial relationships to disclose
Introduction/Rationale: B cells expressing the pro-inflammatory transcription factor T-bet have been implicated in a variety of disease states, including obesity, aging, and autoimmunity. The dependence of this subset on innate signaling via TLR7/9 agonism in the presence of IFNg and IL-21 has been well characterized. However, less is known about the metabolic requirements that may sustain this population during chronic inflammation. Our laboratory has observed that CD11c+ T-bet+ B cells from murine tissues express high levels of the scavenger receptor/fatty acid translocase CD36, suggesting a critical role for this receptor in T-bet+ B cell differentiation and/or function.
Methods: To investigate the role of CD36 in this subset, a B cell-specific CD36 knockout was generated using Cre-Lox recombination. Splenic B cells from control or knockout mice were stimulated in vitro with the TLR7 agonist R848, oxLDL, or both. Flow cytometry was used to assess B cell expression of T-bet, CD36, CD86, and MHC-II. Reactive oxygen species (ROS) were also measured using CellROX Green. In vivo, expansion of splenic CD11c+ T-bet+ B cells was evaluated following R848 administration or high-fat diet (HFD) feeding.
Results: We found that in vitro, R848 drives T-bet and CD36 expression in B cells, resulting in intracellular accumulation of neutral lipids. B cells lacking CD36 had reduced levels of CD86, but not MHC-II, after stimulation with oxLDL, R848, or their combination. Cellular ROS levels, however, were not impacted by CD36 deletion in any stimulation condition. In vivo, deletion of CD36 from B cells was also found to significantly and selectively limit the expansion of splenic CD11c+ T-bet+ B cells following administration of R848, or after HFD.
Conclusion: Taken together, these findings implicate CD36 as a metabolic regulator of T-bet+ B cell differentiation and activation. Further work will delineate how CD36 integrates lipid uptake with immune signaling to shape T-bet+ B cell responses during chronic inflammation.
