3020-LB: Adipocyte- and Preadipocyte-Mediated Regulation of IL-10 Production by B Lymphocytes

Introduction and Objective: Adipose tissue (AT) inflammation, a hallmark of obesity, promotes metabolic disorders such as type 2 diabetes. B-1 cells, an innate-like B cell subset, mitigate diet-induced AT inflammation, in part via the anti-inflammatory cytokine interleukin (IL)-10, whereas B-2 cells, comprised of follicular B cells and marginal zone B cells, exacerbate AT inflammation. Whether mechanistic relationships link AT and B cell function remains a major knowledge gap in this field. The objective of this study was to investigate whether adipocytes and preadipocytes can regulate IL-10 production by B cells. Methods: I.29µ+ B cells (murine B cell lymphoma with B-1 characteristics) and murine splenic B cells (predominantly follicular B-2 cells) were separately cultured for various intervals with or without lipopolysaccharide (LPS) stimulation, in control media or conditioned media prepared from murine 3T3-L1 adipocytes and preadipocytes. IL-10 production by B cells was assessed by real-time RT-PCR and ELISA. Data obtained for conditioned media and control media cultures were compared using t-tests. Results: Conditioned media from both 3T3-L1 adipocytes and preadipocytes increased IL-10 production by LPS-stimulated splenic B cells. Both sources of conditioned media induced IL-10 secretion by I.29µ+ B cells, but diminished IL-10 production by LPS-activated I.29µ+ B cells. This inhibitory effect was not abrogated by 0.1-micron filtration of conditioned media. Conclusion: These data indicate that adipocytes and preadipocytes can regulate IL-10 production by B cells. Further, the results suggest this regulatory effect can be positive or negative depending on the type of B cell and its activation status and is mediated by a soluble factor(s) < 0.1-micron rather than exosomes. These findings support the hypothesis that AT can influence anti-inflammatory functions of B cells and warrant further studies of adipocyte and preadipocyte communication with primary B-1 and B-2 cells. Disclosure J.W. Brewer: None. O.L. Doud: None. R. Josepher: None. C. Leeling: None. C. Lovelady: None. K. Sparkman: None. R.L. Judd: None.