A unique population of IgG-expressing plasma cells lacking CD19 is enriched in human bone marrow
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, 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
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 they carried a prosurvival, distinctly mature phenotype, that is, HLA-DR(low)Ki-67(-)CD95(low)CD28(+)CD56(+/-), with increased BCL2 and they 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, that is, 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 multilayer 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.
© 2015 by The American Society of Hematology.
Source: PubMed