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J Immunol. 2017 Jun 15;198(12):4618-4628. doi: 10.4049/jimmunol.1501761. Epub 2017 May 10.

Early Emergence of CD19-Negative Human Antibody-Secreting Cells at the Plasmablast to Plasma Cell Transition.

Author information

1
Section of Experimental Musculoskeletal Medicine, Leeds Institute of Rheumatic and Musculoskeletal Medicine, St James's University Hospital, Leeds LS9 7TF, United Kingdom.
2
Section of Experimental Haematology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, United Kingdom; and.
3
Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals National Health Service Trust, St James's University Hospital, Leeds LS9 7TF, United Kingdom.
4
Section of Experimental Haematology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, United Kingdom; and r.tooze@leeds.ac.uk.

Abstract

Long-lived human plasma cells (PCs) play central roles in immunity and autoimmunity and are enriched among the subpopulation of CD19neg human PCs. However, whether human CD19neg 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 CD19neg plasmablasts, the proliferative precursor state to mature PCs, and demonstrate by ELISPOT that these are Ab-secreting cells (ASCs). During the acute response to influenza vaccination, CD19pos, CD19low, and CD19neg ASCs secrete vaccine-specific Abs and show linked IGHV repertoires. To address precursor/product relationships, we use in vitro models that mimic T-dependent and T-independent differentiation, finding that the CD19neg state can be established at the plasmablast to PC transition, that CD19neg PCs increase as a percentage of surviving PCs in vitro, and that CD19neg and CD19pos PCs can be maintained independently. These data provide proof-of-principle for the view that newly generated ASCs can acquire a mature PC phenotype that is accompanied by loss of CD19 expression at an early stage of differentiation and that aging is not an obligate requirement for a CD19neg state to be established.

PMID:
28490574
PMCID:
PMC5458329
DOI:
10.4049/jimmunol.1501761
[Indexed for MEDLINE]
Free PMC Article

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