ORIGINAL RESEARCH article
Front. Immunol.
Sec. B Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1644102
This article is part of the Research TopicDecoding the Spectrum of Plasma Cell Heterogeneity: Insights into Maturity and LongevityView all articles
Maturation of Human Early-Minted Blood Antibody-Secreting Cells is Coupled with Increased IgG Secretion Rates
Provisionally accepted
Doan C Nguyen*
Ian T HentenaarMonica Cabrera-MoraShuya KyuAndrea Morrison- Porter
Natalie S HaddadJoel AndrewsDanielle RobertsSagar Lonial
Ignacio Sanz
F. Eun-Hyung Lee- Emory University, Atlanta, United States
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FEL is the founder of Micro-Bplex, Inc. and BeaconDx, Inc., serves on the scientific board of Be Biopharma, is a recipient of grants from the BMGF and Genentech, Inc., and has served as a consultant for Astra Zeneca. IS has consulted for GSK, Pfizer, Kayverna, Johnson & Johnson, Celgene, Bristol Myer Squibb, and Visterra. FEL, DCN, and IS are inventors of the patents concerning the plasma cell survival media related to this work (including US11124766B2, US11125757B2, US12163965B2, and US12173315B2). The other authors declare no conflicts of interest.Plasma cells are known antibody-secreting factories with immunoglobulin (Ig) transcripts that increase as the cell matures into a long-lived plasma cell (LLPC) in the bone marrow (BM).Whether the Ig secretion rates among human antibody-secreting cells (ASC) are homogeneous or BM LLPC are capable of secreting more antibodies per cell compared to early-minted blood ASC remain unclear. Here, we use bulk and single cell cultures in a novel in vitro BM mimetic survival system to measure the IgG secretion rates of human ASC. We find that the mature BM ASC produce more IgG molecules per cell compared to immature, early-minted blood ASC.Furthermore, these blood ASC can mature into LLPC phenotypes in culture, and we show that ASC on day 7 secrete more IgG per cell than the input ASC from day 0. Thus, as human ASC mature, they increase the number of Ig transcripts and result in higher Ig secretion. These results also demonstrate that the mature ASC in the BM have higher Ig secretion rates compared to early-minted blood ASC.
Keywords: Antibody-secreting cell, Plasma cell, Blood, Bone Marrow, maturation
Received: 09 Jun 2025; Accepted: 07 Aug 2025.
Copyright: © 2025 Nguyen, Hentenaar, Cabrera-Mora, Kyu, Morrison- Porter, Haddad, Andrews, Roberts, Lonial, Sanz and Lee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Doan C Nguyen, Emory University, Atlanta, United States
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