ATP-degrading ENPP1 is required for survival (or persistence) of long-lived plasma cells

Hongsheng Wang; Ines Gonzalez-Garcia; Javier Traba; Shweta Jain; Solomon Conteh; Dong-Mi Shin; Chenfeng Qi; Yuanyuan Gao; Jiafang Sun; Sungyun Kang; Sadia Abbasi; Zohreh Naghashfar; Jeongheon Yoon; Wendy DuBois; Alexander L Kovalchuk; Michael N Sack; Patrick Duffy; Herbert C Morse 3rd

doi:10.1038/s41598-017-18028-z

ATP-degrading ENPP1 is required for survival (or persistence) of long-lived plasma cells

Sci Rep. 2017 Dec 19;7(1):17867. doi: 10.1038/s41598-017-18028-z.

Authors

Hongsheng Wang¹, Ines Gonzalez-Garcia^{2

3}, Javier Traba⁴, Shweta Jain², Solomon Conteh⁵, Dong-Mi Shin⁶, Chenfeng Qi², Yuanyuan Gao², Jiafang Sun², Sungyun Kang^{2

7}, Sadia Abbasi², Zohreh Naghashfar², Jeongheon Yoon^{2

8}, Wendy DuBois⁹, Alexander L Kovalchuk², Michael N Sack⁴, Patrick Duffy⁵, Herbert C Morse 3rd¹⁰

Affiliations

¹ Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA. wanghongs@niaid.nih.gov.
² Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA.
³ Celgene Institute of Translational Research Europe, Parque Tecnológico Cartuja 93, c/Isaac Newton n.4, E-41092, Seville, Spain.
⁴ Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, 20814, USA.
⁵ Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA.
⁶ Department of Food and Nutrition, Seoul National University, Seoul, 151-742, Korea.
⁷ Department of Biology, Indiana University, Myers Hall 230, 915 E. 3rd St., Bloomington, IN, 47405, USA.
⁸ Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814, USA.
⁹ Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20814, USA.
¹⁰ Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA. hmorse@niaid.nih.gov.

Abstract

Survival of antibody-secreting plasma cells (PCs) is vital for sustained antibody production. However, it remains poorly understood how long-lived PCs (LLPCs) are generated and maintained. Here we report that ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is preferentially upregulated in bone marrow LLPCs compared with their splenic short-lived counterparts (SLPCs). We studied ENPP1-deficient mice (Enpp1 ^-/- ) to determine how the enzyme affects PC biology. Although Enpp1 ^-/- mice generated normal levels of germinal center B cells and plasmablasts in periphery, they produced significantly reduced numbers of LLPCs following immunization with T-dependent antigens or infection with plasmodium C. chabaudi. Bone marrow chimeric mice showed B cell intrinsic effect of ENPP1 selectively on generation of bone marrow as well as splenic LLPCs. Moreover, Enpp1 ^-/- PCs took up less glucose and had lower levels of glycolysis than those of wild-type controls. Thus, ENPP1 deficiency confers an energetic disadvantage to PCs for long-term survival and antibody production.

Publication types

Research Support, N.I.H., Intramural

MeSH terms

Adenosine Triphosphate / metabolism*
Animals
Antibody Formation / immunology
B-Lymphocytes / metabolism
Bone Marrow / metabolism
Bone Marrow Cells / metabolism
Cell Survival / physiology
Cells, Cultured
Germinal Center / metabolism
Glucose / metabolism
Glycolysis / physiology
Humans
Mice
Mice, Inbred C57BL
Phosphoric Diester Hydrolases / metabolism*
Plasma Cells / metabolism*
Pyrophosphatases / metabolism*
Spleen / metabolism
Up-Regulation / physiology

Substances

Adenosine Triphosphate
Phosphoric Diester Hydrolases
ectonucleotide pyrophosphatase phosphodiesterase 1
Pyrophosphatases
Glucose