Metabolic and Transcriptional Modules Independently Diversify Plasma Cell Lifespan and Function

Cell Reports
Wing Y LamDeepta Bhattacharya

Abstract

Plasma cell survival and the consequent duration of immunity vary widely with infection or vaccination. Using fluorescent glucose analog uptake, we defined multiple developmentally independent mouse plasma cell populations with varying lifespans. Long-lived plasma cells imported more fluorescent glucose analog, expressed higher surface levels of the amino acid transporter CD98, and had more autophagosome mass than did short-lived cells. Low amino acid concentrations triggered reductions in both antibody secretion and mitochondrial respiration, especially by short-lived plasma cells. To explain these observations, we found that glutamine was used for both mitochondrial respiration and anaplerotic reactions, yielding glutamate and aspartate for antibody synthesis. Endoplasmic reticulum (ER) stress responses, which link metabolism to transcriptional outcomes, were similar between long- and short-lived subsets. Accordingly, population and single-cell transcriptional comparisons across mouse and human plasma cell subsets revealed few consistent and conserved differences. Thus, plasma cell antibody secretion and lifespan are primarily defined by non-transcriptional metabolic traits.

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Citations

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Datasets Mentioned

BETA
GSE115860

Methods Mentioned

BETA
glycosylation
transgenic
RNA-seq
total hip arthroplasty
fluorescence activated cell sorting
Fluorescence-activated cell sorting
FACS
ELISA
flow cytometry
PCR

Key Resources (RRID) Mentioned

AB_10915989
AB_2340507
AB_313007
AB_2044012
AB_10643763
AB_1727535
AB_2561393
AB_2562565
AB_2619605
AB_394889

Software Mentioned

AMT Image Capture Engine
Cell Ranger
Prism
DESeq2
ImageJ
fastq
Access
Mixcr
SeqGeq
Clonoplot

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