The Role of CD38 on the Function of Regulatory B Cells in a Murine Model of Lupus

Burlock, Brianna; Richardson, Gabrielle; García-Rodríguez, Sonia; Guerrero, Salvador; Zubiaur, Mercedes; Sancho, Jaime

doi:10.3390/ijms19102906

Open AccessArticle

The Role of CD38 on the Function of Regulatory B Cells in a Murine Model of Lupus

by

Brianna Burlock

^1,†,

Gabrielle Richardson

^1,†,

Sonia García-Rodríguez

¹,

Salvador Guerrero

²,

Mercedes Zubiaur

¹

and

Jaime Sancho

^1,*

¹

Department of Cellular Biology and Immunology, Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), 18016 Granada, Spain

²

Flow-Cytometry Unit, IPBLN-CSIC, 18016 Granada, Spain

^*

Author to whom correspondence should be addressed.

^†

These authors equally contributed to this work.

Int. J. Mol. Sci. 2018, 19(10), 2906; https://doi.org/10.3390/ijms19102906

Submission received: 22 August 2018 / Revised: 17 September 2018 / Accepted: 18 September 2018 / Published: 25 September 2018

(This article belongs to the Special Issue B Cells and Immunological Tolerance)

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Abstract

Previous work from our group has shown that Cd38^−/− mice develop a milder pristane-induced lupus disease than WT or Art2^−/− counterparts, demonstrating a new role for CD38 in promoting aberrant inflammation and lupus-like autoimmunity via a Transient Receptor Potential Melastatin 2 (TRPM2)-dependent apoptosis-driven mechanism. In this study we asked whether CD38 may play a role in the expression and function of regulatory B cells (IL-10-producing B cells or B10 cells). In pristane-treated mice the frequency of spleen CD19⁺CD1d^hiCD5⁺ B cells, which are highly enriched in B10 cells, was significantly increased in Cd38^−/− splenocytes compared to WT, while the frequency of peritoneal plasmacytoid dendritic cells (pDCs), which are major type I Interferon (IFN) producers, was greatly diminished. The low proportion of pDCs correlated with lower amounts of IFN-α in the peritoneal lavage fluids of the Cd38^−/− mice than of WT and Art2^−/− mice. Functional ex vivo assays showed increased frequencies of IL-10-producing B cells in Cd38^−/− splenocytes than in WT upon stimulation with an agonist anti-CD40 mAb. Overall these results strongly suggest that Cd38^−/− mice are better suited than WT mice to generate and expand regulatory B10 cells following the appropriate stimulation.

Keywords: Bregs; CD38; CD1d^hi; lupus; IL-10; autoimmunity; inflammation

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MDPI and ACS Style

Burlock, B.; Richardson, G.; García-Rodríguez, S.; Guerrero, S.; Zubiaur, M.; Sancho, J. The Role of CD38 on the Function of Regulatory B Cells in a Murine Model of Lupus. Int. J. Mol. Sci. 2018, 19, 2906. https://doi.org/10.3390/ijms19102906

AMA Style

Burlock B, Richardson G, García-Rodríguez S, Guerrero S, Zubiaur M, Sancho J. The Role of CD38 on the Function of Regulatory B Cells in a Murine Model of Lupus. International Journal of Molecular Sciences. 2018; 19(10):2906. https://doi.org/10.3390/ijms19102906

Chicago/Turabian Style

Burlock, Brianna, Gabrielle Richardson, Sonia García-Rodríguez, Salvador Guerrero, Mercedes Zubiaur, and Jaime Sancho. 2018. "The Role of CD38 on the Function of Regulatory B Cells in a Murine Model of Lupus" International Journal of Molecular Sciences 19, no. 10: 2906. https://doi.org/10.3390/ijms19102906

APA Style

Burlock, B., Richardson, G., García-Rodríguez, S., Guerrero, S., Zubiaur, M., & Sancho, J. (2018). The Role of CD38 on the Function of Regulatory B Cells in a Murine Model of Lupus. International Journal of Molecular Sciences, 19(10), 2906. https://doi.org/10.3390/ijms19102906

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The Role of CD38 on the Function of Regulatory B Cells in a Murine Model of Lupus

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