Dissecting the role of CD36 on tbet+ b cells during obesity and autoimmunity - CD21-CD23- CD11C+ tbet+ age associated b cells or abcs, expand in primary immune and peripheral tissues during chronic…

The National Institute of Allergy and Infectious Diseases awarded The University of Texas Health Science Center at San Antonio $421,223 on February 5, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to investigate the role of CD36 on T-bet+ B cells during obesity and autoimmunity.

The research dissects how age-associated B cells (ABCs)—CD21−CD23− CD11C+ T-bet+ cells that expand in primary immune and peripheral tissues during chronic conditions including aging, autoimmune diseases, atherosclerosis, and obesity—drive autoimmunity and metabolic dysfunction. ABCs produce IgG2a/c autoantibodies that exacerbate these conditions and inhibit germinal center responses to conventional antigens, potentially explaining poor vaccine outcomes in elderly, autoimmune, and obese populations. The project examines the previously unreported high expression of CD36, a class B scavenger receptor and fatty acid translocase, on ABC cells and its role in ABC expansion during obesity and inflammatory stimulation. The research explores whether CD36 mediates innate signaling, antigen uptake, or metabolic reprogramming through fatty acid uptake and PPAR-β signaling to support mitochondrial oxidative phosphorylation.

Work is performed in San Antonio, Texas, with a period of performance through January 31, 2028. This is a Project Grant, the standard NIH assistance type for investigator-initiated research.

Dissecting the role of CD36 on tbet+ b cells during obesity and autoimmunity - CD21-CD23- CD11C+ tbet+ age associated b cells or abcs, expand in primary immune and peripheral tissues during chronic conditions such as aging, autoimmune diseases, atherosclerosis, and obesity. These abcs largely produce IGG2A/c autoantibodies which exacerbate autoimmunity and metabolic dysfunction, positioning them as a promising therapeutic target for a broad array of inflammatory and infectious diseases. Furthermore, abcs have recently been found to inhibit germinal center responses to conventional antigens such as those in most effective vaccines, which could explain the poor vaccine outcomes in elderly, autoimmune, and obese patients. As such, this suggests that blocking abcs may improve vaccine responses across a broad array of platforms. Abcs expand in vitro and in vivo in response to a combination of TLR agonists, cytokines like ifng and IL-21 as well as CD4+ t cell help, but the nature and coordination of signals which mediate ABC expansion and effector function remain inadequately understood. We recently discovered that ABC cells express unexpectedly high levels of class b scavenger receptor and fatty acid translocase CD36. Even more interesting, expansion of abcs during obesity or in response to TLR7 inflammatory stimulation requires CD36, suggesting a role for CD36 in stimulation or maintenance of this unique b cell subset during chronic inflammation of obesity and autoimmunity. CD36 is capable of a myriad of different roles, including innate signaling, efficient uptake of antigen and metabolic reprograming, any one of which could be contributing to ABC activity. For example, CD36 mediated fatty acid uptake and subsequent ppar-beta signaling support mitochondrial oxidative phosphorylation over glycolysis. In addition to mediating lipid uptake for metabolic regulation, CD36 also binds long chain fatty acids including oxidized phospholipids and pattern associated molecular patterns (damps/pamps) such as apoptotic cells and amyloid proteins which could be presented by MHC II to engage helper t cells. CD36 engagement also triggers intracellular signaling cascades leading to innate activation and secretion of inflammatory cytokines. This project aims to combine unique mouse strains engineered to lack CD36 selectively in b cells with inflammatory in vivo mouse models to determine the relative contribution of CD36 to mediating antigen uptake and presentation, innate immune activation, and metabolic engagement by ABC cells during obesity or autoimmune disease. Elaborating a better understanding of signals employed by CD36 during activation of abcs will allow targeted clinical interventions to slow their inflammatory contribution to disease and also improve immune responses to vaccination or infection for patients with obesity, autoimmune disease, or related chronic inflammatory conditions.