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Early Emergence of CD19-Negative Human Antibody-Secreting Cells at the Plasmablast to Plasma Cell Transition
Ist Teil von
The Journal of immunology (1950), 2017-06, Vol.198 (12), p.4618-4628
Ort / Verlag
United States: American Association of Immunologists
Erscheinungsjahr
2017
Quelle
MEDLINE
Beschreibungen/Notizen
Long-lived human plasma cells (PCs) play central roles in immunity and autoimmunity and are enriched among the subpopulation of CD19
human PCs. However, whether human CD19
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
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, CD19
, CD19
, and CD19
ASCs secrete vaccine-specific Abs and show linked
repertoires. To address precursor/product relationships, we use in vitro models that mimic T-dependent and T-independent differentiation, finding that the CD19
state can be established at the plasmablast to PC transition, that CD19
PCs increase as a percentage of surviving PCs in vitro, and that CD19
and CD19
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 CD19
state to be established.