Arumugakani, G, Stephenson, SJ, Newton, DJ orcid.org/0000-0002-0214-1486 et al. (5 more authors) (2017) Early emergence of CD19-negative human antibody secreting cells at the plasmablast to plasma cell transition. Journal of Immunology, 198 (12). pp. 4618-4628. ISSN 0022-1767
Abstract
Long-lived human plasma cells (PCs) play central roles in immunity and autoimmunity and are enriched amongst the subpopulation of CD19-negative human PCs. However, whether human CD19-negative PCs are necessarily ″aged″ cells that have gradually lost CD19 expression is not known. Assessing peripheral blood samples at steady state and during the acute response to influenza vaccination in healthy donors we identify the presence of phenotypic CD19-negative plasmablasts, the proliferative precursor state to mature PCs, and demonstrate by ELISpot that these are antibody-secreting cells (ASCs). During the acute response to influenza vaccination CD19-positive, CD19-low and CD19-negative ASCs secrete vaccine-specific antibody and show linked IGHV repertoires. To address precursor/product relationships we employ in vitro models which mimic both T-dependent and T-independent differentiation finding that the CD19-negative state can be established at the plasmablast to PC transition, that CD19-negative PCs increase as a percentage of surviving PCs in vitro, and that CD19-negative and CD19-positive PCs can be maintained independently. These data provide proof-of-principle for the view that newly generated ASCs can acquire a mature PC phenotype accompanied by loss of CD19 expression at an early stage of differentiation and that ″aging″ is not an obligate requirement for a CD19-negative state to be established.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2017, The Authors. This article is distributed under the terms of the CC BY 4.0 Unported license [https://creativecommons.org/licenses/by/4.0/]. |
Keywords: | Human; Plasma cell; Plasmablast; CD19; Immune Response; Influenza |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Experimental Haematology (Leeds) |
Funding Information: | Funder Grant number Cancer Research UK C7845/A10066 National Inst for Health Research (NIHR) NONE GIVEN Cancer Research UK C7845/A17723 |
Depositing User: | Symplectic Publications |
Date Deposited: | 26 Apr 2017 12:42 |
Last Modified: | 23 Jun 2023 22:28 |
Status: | Published |
Publisher: | American Association of Immunologists |
Identification Number: | 10.4049/jimmunol.1501761 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:115606 |