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A unique population of IgG-expressing plasma cells lacking CD19 is enriched in human bone marrow.

Journal article
Authors Henrik E Mei
Ina Wirries
Daniela Frölich
Mikael Brisslert
Claudia Giesecke
Joachim R Grün
Tobias Alexander
Stefanie Schmidt
Katarzyna Luda
Anja A Kühl
Robby Engelmann
Michael Dürr
Tobias Scheel
Maria Bokarewa
Carsten Perka
Andreas Radbruch
Thomas Dörner
Published in Blood
Volume 125
Issue 11
ISSN 1528-0020
Publication year 2015
Published at Institute of Medicine, Department of Rheumatology and Inflammation Research
Language en
Links dx.doi.org/10.1182/blood-2014-02-55...
Subject categories Clinical Medicine

Abstract

Specific serum antibodies mediating humoral immunity and autoimmunity are provided by mature plasma cells (PC) residing in the bone marrow (BM), yet their dynamics and composition are largely unclear. We here characterize distinct subsets of human PC differing by CD19 expression. Unlike CD19(+) PC, CD19(-) PC were restricted to BM, expressed predominantly IgG and carried a pro-survival, distinctly mature phenotype, i.e. HLA-DR(low)Ki-67(-)CD95(low)CD28(+)CD56(+/-), with increased BCL2 and resisted their mobilization from the BM after systemic vaccination. Fewer mutations within immunoglobulin VH rearrangements of CD19(-) BMPC may indicate their differentiation in early life. Their resistance to in vivo B cell depletion, i.e. their independency from supply with new plasmablasts is consistent with long-term stability of this PC subset in the BM. Moreover, CD19(-) PC were detectable in chronically inflamed tissues and secreted autoantibodies. We propose a multi-layer model of PC memory in which CD19(+) and CD19(-) PC represent dynamic and static components, respectively, permitting both adaptation and stability of humoral immune protection.

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