Positive Health Online

Abstract

DI CARO and COLLEAGUES,  (1)Department of Pediatrics, Division of Immunogenetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; RiMed Foundation, Palermo, Italy studied the effects of human tolerogenic dendritic cells upon the proliferation of immunosuppressive B lymphocytes.

Background

While much is known about tolerogenic dendritic cell effects on forkhead box protein 3 (FoxP3)⁺ regulatory T cells, virtually nothing is known about their effects on another arm of immunoregulation that is mediated by a subpopulation of immunosuppressive B cells.

Methodology

These cells suppress rheumatoid arthritis, lupus and inflammatory bowel disease in mice, and functional defects have been reported in human lupus.

Results

We show that co-stimulation-impaired tolerogenic dendritic cells that prevent and reverse type 1 diabetes mellitus induce the proliferation of human immunosuppressive B cells in vitro. We also show that the suppressive properties of these B cells concentrate inside the CD19⁺ CD24⁺ B cell population and more specifically inside the CD19⁺ CD24⁺ CD38⁺ regulatory B cell population. We discovered that B cell conversion into suppressive cells in vitro is partially dependent on dendritic cell production of retinoic acid and also that CD19⁺ CD24⁺ CD38⁺ B regulatory cells express retinoic acid receptors.

Conclusion

Taken together, our data suggest a model whereby part of the immunosuppressive properties of human tolerogenic dendritic cells could be mediated by retinoic acid which, in addition to its known role in favouring T cell differentiation to FoxP3⁺ regulatory T cells, acts to convert B cells into immunosuppressive cells.

References

Di Caro V(1), Phillips B, Engman C, Harnaha J, Trucco M, Giannoukakis N. Retinoic acid-producing, ex-vivo-generated human tolerogenic dendritic cells induce the proliferation of immunosuppressive B lymphocytes.  Clin Exp Immunol. 174(2):302-17. doi: 10.1111/cei.12177. Nov 2013.