Lasting antibody responses are mediated by a combination of newly formed and established bone marrow plasma cells drawn from clonally distinct precursors

I Chernova, DD Jones, JR Wilmore… - The Journal of …, 2014 - journals.aai.org
I Chernova, DD Jones, JR Wilmore, A Bortnick, M Yucel, U Hershberg, D Allman
The Journal of Immunology, 2014journals.aai.org
Current models hold that serum Ab titers are maintained chiefly by long-lived bone marrow
(BM) plasma cells (PCs). In this study, we characterize the role of subpopulations of BM PCs
in long-term humoral responses to T cell–dependent Ag. Surprisingly, our results indicate
that 40–50% of BM PCs are recently formed cells, defined, in part, by rapid steady-state
turnover kinetics and secretion of low-affinity IgM Abs. Further, for months after immunization
with a hapten–protein conjugate, newly formed Ag-induced, IgM-secreting BM PCs were …
Abstract
Current models hold that serum Ab titers are maintained chiefly by long-lived bone marrow (BM) plasma cells (PCs). In this study, we characterize the role of subpopulations of BM PCs in long-term humoral responses to T cell–dependent Ag. Surprisingly, our results indicate that 40–50% of BM PCs are recently formed cells, defined, in part, by rapid steady-state turnover kinetics and secretion of low-affinity IgM Abs. Further, for months after immunization with a hapten–protein conjugate, newly formed Ag-induced, IgM-secreting BM PCs were detected in parallel with longer-lived IgG-secreting cells, suggesting ongoing and parallel input to the BM PC pool from two distinct pools of activated B cells. Consistent with this interpretation, IgM and IgG Abs secreted by cells within distinct PC subsets exhibited distinct L chain usage. We conclude that long-term Ab responses are maintained by a dynamic BM PC pool composed of both recently formed and long-lived PCs drawn from clonally disparate precursors.
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