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

作者:Mei Henrik E*; Wirries Ina; Froelich Daniela; Brisslert Mikael; Giesecke Claudia; Gruen Joachim R; Alexander Tobias; Schmidt Stefanie; Luda Katarzyna; Kuehl Anja A; Engelmann Robby; Duerr Michael; Scheel Tobias; Bokarewa Maria; Perka Carsten; Radbruch Andreas; Doerner Thomas
来源:Blood, 2015, 125(11): 1739-1748.
DOI:10.1182/blood-2014-02-555169

摘要

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 V-H 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 auto-antibodies. 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.

  • 出版日期2015-3-12