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

HE Mei, I Wirries, D Frölich, M Brisslert… - Blood, The Journal …, 2015 - ashpublications.org
HE Mei, I Wirries, D Frölich, M Brisslert, C Giesecke, JR Grün, T Alexander, S Schmidt…
Blood, The Journal of the American Society of Hematology, 2015ashpublications.org
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-
DRlowKi-67− CD95lowCD28+ CD56+/−, with increased BCL2 and they resisted their …
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-DRlowKi-67CD95lowCD28+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.
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