한빛사논문
- 조회430
Meixue Duan 1, Doan C. Nguyen 2,13, Chester J. Joyner 2,11,13, Celia L. Saney 2,11, Christopher M. Tipton 2,3, Joel Andrews 4, Sagar Lonial 4, Caroline Kim 2, Ian Hentenaar 2, Astrid Kosters 3, Eliver Ghosn 3, Annette Jackson 5,6, Stuart Knechtle 6, Stalinraja Maruthamuthu 7, Sindhu Chandran 8, Tom Martin 8, Raja Rajalingam 7, Flavio Vincenti 9, Cynthia Breeden 10, Ignacio Sanz 3, Greg Gibson 1,12, F. Eun-Hyung Lee 2,3,12,14
1School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA
2Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University, Atlanta, GA, USA
3Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA
4Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
5Departments of Immunology, Duke University, Durham, NC, USA
6Department of Surgery, Duke University, Durham, NC, USA
7Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California San Francisco, San Francisco, CA, USA
8Department of Medicine, University of California San Francisco, San Francisco, CA, USA
9Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA
10Emory Transplant Center, Department of Surgery, School of Medicine, Emory University, Atlanta, GA, USA
11Present address: Center for Vaccines and Immunology, Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA
12Senior author
13These authors contributed equally
14Lead contact
Corresponding author : F. Eun-Hyung Lee
Abstract
Human bone marrow (BM) plasma cells are heterogeneous, ranging from newly arrived antibody-secreting cells (ASCs) to long-lived plasma cells (LLPCs). We provide single-cell transcriptional resolution of 17,347 BM ASCs from five healthy adults. Fifteen clusters are identified ranging from newly minted ASCs (cluster 1) expressing MKI67 and high major histocompatibility complex (MHC) class II that progress to late clusters 5-8 through intermediate clusters 2-4. Additional ASC clusters include the following: immunoglobulin (Ig) M predominant (likely of extra-follicular origin), interferon responsive, and high mitochondrial activity. Late ASCs are distinguished by G2M checkpoints, mammalian target of rapamycin (mTOR) signaling, distinct metabolic pathways, CD38 expression, utilization of tumor necrosis factor (TNF)-receptor superfamily members, and two distinct maturation pathways involving TNF signaling through nuclear factor κB (NF-κB). This study provides a single-cell atlas and molecular roadmap of LLPC maturation trajectories essential in the BM microniche. Altogether, understanding BM ASC heterogeneity in health and disease enables development of new strategies to enhance protective ASCs and to deplete pathogenic ones.
논문정보
- Research article
- 2023년 06월 (BRIC 등록일 2023-07-06)
- 국외 연구진
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