Open AccessATP-degrading ENPP1 is required for survival (or persistence) of long-lived plasma cells
Author(s) -
Hongsheng Wang,
Inés González-Garcı́a,
Javier Traba,
Shweta Jain,
Solomon Conteh,
DongMi Shin,
ChenFeng Qi,
Yuanyuan Gao,
Jiafang Sun,
Sungyun Kang,
Sadia Abbasi,
Zohreh Naghashfar,
Jeongheon Yoon,
Wendy Dubois,
Alexander L. Kovalchuk,
Michael N. Sack,
Patrick E. Duffy,
Herbert C. Morse
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-18028-z
Subject(s) - persistence (discontinuity) , biology , engineering , geotechnical engineering
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.