Graduate student UT Health San Antonio San Antonio, Texas, United States
Disclosure(s):
Emma Collins: No financial relationships to disclose
Introduction/Rationale: CD21- CD23- CD11c+ Tbet+ B cells expand in primary immune and peripheral tissues during chronic conditions such as aging, autoimmune diseases, and obesity. These antigen experienced B cells largely produce IgG2a/c autoantibodies which exacerbate autoimmunity and metabolic dysfunction, positioning them as a promising therapeutic target. Typically, Tbet+ CD11c+ B cells expand in vitro and in vivo in response to a combination of TLR agonists, cytokines, and CD4+ T cell help, but the nature and coordination of signals involved in their expansion and effector function remain poorly understood. We have discovered that Tbet+ CD11c+ B cells express high levels of class B scavenger receptor and fatty acid translocase CD36. CD36 is capable of innate signaling, antigen uptake and metabolic reprogramming, all of which could be contributing to B cell activity.
Methods: This project combines unique mouse strains engineered to lack CD36 selectively in B cells with high fat diet-induced obesity or bm12 autoimmune mouse models. We are determining the relative contribution of CD36 to Tbet+CD11c+ B cell expansion and effector function.
Results: Mice lacking CD36 in B cells fail to expand inflammatory CD11c+Tbet+ B cells or accompanying splenic TFH/TPH cells to the same level as BWT controls during high fat diet-induced obesity. HFD-fed obese mice lacking CD36 on B cells also develop significantly lower levels of anti-oxLDL and anti-dsDNA IgG2c autoantibodies than WT control mice. This effect may extend to additional effector functions including antibodies and cytokine production. We will also determine if Tbet+ B cell dependence on CD36 extends to cGVHD lupus mice.
Conclusion: Elaborating a better understanding of signals employed by CD36 during expansion and function of CD11c+Tbet+ B cells will allow targeted clinical interventions and could improve immune responses to vaccination or infection for patients with obesity, autoimmunity, or related chronic inflammatory conditions.
