Stage-Specific Non-Coding RNA Expression Patterns during In Vitro Human B Cell Differentiation into Antibody Secreting Plasma Cells

The differentiation of B cells into antibody secreting plasma cells (PCs) is governed by a strict regulatory network that results in expression of specific transcriptomes along the activation continuum. In vitro models yielding significant numbers of PCs phenotypically identical to the in vivo state...

Full description

Bibliographic Details
Main Authors: Renee C. Tschumper, Dominique B. Hoelzinger, Denise K. Walters, Jaime I. Davila, Collin A. Osborne, Diane F. Jelinek
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Non-Coding RNA
Subjects:
Online Access:https://www.mdpi.com/2311-553X/8/1/15
_version_ 1797477551860350976
author Renee C. Tschumper
Dominique B. Hoelzinger
Denise K. Walters
Jaime I. Davila
Collin A. Osborne
Diane F. Jelinek
author_facet Renee C. Tschumper
Dominique B. Hoelzinger
Denise K. Walters
Jaime I. Davila
Collin A. Osborne
Diane F. Jelinek
author_sort Renee C. Tschumper
collection DOAJ
description The differentiation of B cells into antibody secreting plasma cells (PCs) is governed by a strict regulatory network that results in expression of specific transcriptomes along the activation continuum. In vitro models yielding significant numbers of PCs phenotypically identical to the in vivo state enable investigation of pathways, metabolomes, and non-coding (ncRNAs) not previously identified. The objective of our study was to characterize ncRNA expression during human B cell activation and differentiation. To achieve this, we used an in vitro system and performed RNA-seq on resting and activated B cells and PCs. Characterization of coding gene transcripts, including immunoglobulin (Ig), validated our system and also demonstrated that memory B cells preferentially differentiated into PCs. Importantly, we identified more than 980 ncRNA transcripts that are differentially expressed across the stages of activation and differentiation, some of which are known to target transcription, proliferation, cytoskeletal, autophagy and proteasome pathways. Interestingly, ncRNAs located within Ig loci may be targeting both Ig and non-Ig-related transcripts. ncRNAs associated with B cell malignancies were also identified. Taken together, this system provides a platform to study the role of specific ncRNAs in B cell differentiation and altered expression of those ncRNAs involved in B cell malignancies.
first_indexed 2024-03-09T21:19:19Z
format Article
id doaj.art-e4b126b878d84e90930c0886e96b0646
institution Directory Open Access Journal
issn 2311-553X
language English
last_indexed 2024-03-09T21:19:19Z
publishDate 2022-02-01
publisher MDPI AG
record_format Article
series Non-Coding RNA
spelling doaj.art-e4b126b878d84e90930c0886e96b06462023-11-23T21:27:19ZengMDPI AGNon-Coding RNA2311-553X2022-02-01811510.3390/ncrna8010015Stage-Specific Non-Coding RNA Expression Patterns during In Vitro Human B Cell Differentiation into Antibody Secreting Plasma CellsRenee C. Tschumper0Dominique B. Hoelzinger1Denise K. Walters2Jaime I. Davila3Collin A. Osborne4Diane F. Jelinek5Department of Immunology, Mayo Clinic, Rochester, MN 55905, USADepartment of Immunology, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USADepartment of Immunology, Mayo Clinic, Rochester, MN 55905, USADepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USADepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905, USADepartment of Immunology, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USAThe differentiation of B cells into antibody secreting plasma cells (PCs) is governed by a strict regulatory network that results in expression of specific transcriptomes along the activation continuum. In vitro models yielding significant numbers of PCs phenotypically identical to the in vivo state enable investigation of pathways, metabolomes, and non-coding (ncRNAs) not previously identified. The objective of our study was to characterize ncRNA expression during human B cell activation and differentiation. To achieve this, we used an in vitro system and performed RNA-seq on resting and activated B cells and PCs. Characterization of coding gene transcripts, including immunoglobulin (Ig), validated our system and also demonstrated that memory B cells preferentially differentiated into PCs. Importantly, we identified more than 980 ncRNA transcripts that are differentially expressed across the stages of activation and differentiation, some of which are known to target transcription, proliferation, cytoskeletal, autophagy and proteasome pathways. Interestingly, ncRNAs located within Ig loci may be targeting both Ig and non-Ig-related transcripts. ncRNAs associated with B cell malignancies were also identified. Taken together, this system provides a platform to study the role of specific ncRNAs in B cell differentiation and altered expression of those ncRNAs involved in B cell malignancies.https://www.mdpi.com/2311-553X/8/1/15non-coding RNAplasma cellsin vitro B cell differentiationhuman B lymphocytesRNA-seq
spellingShingle Renee C. Tschumper
Dominique B. Hoelzinger
Denise K. Walters
Jaime I. Davila
Collin A. Osborne
Diane F. Jelinek
Stage-Specific Non-Coding RNA Expression Patterns during In Vitro Human B Cell Differentiation into Antibody Secreting Plasma Cells
Non-Coding RNA
non-coding RNA
plasma cells
in vitro B cell differentiation
human B lymphocytes
RNA-seq
title Stage-Specific Non-Coding RNA Expression Patterns during In Vitro Human B Cell Differentiation into Antibody Secreting Plasma Cells
title_full Stage-Specific Non-Coding RNA Expression Patterns during In Vitro Human B Cell Differentiation into Antibody Secreting Plasma Cells
title_fullStr Stage-Specific Non-Coding RNA Expression Patterns during In Vitro Human B Cell Differentiation into Antibody Secreting Plasma Cells
title_full_unstemmed Stage-Specific Non-Coding RNA Expression Patterns during In Vitro Human B Cell Differentiation into Antibody Secreting Plasma Cells
title_short Stage-Specific Non-Coding RNA Expression Patterns during In Vitro Human B Cell Differentiation into Antibody Secreting Plasma Cells
title_sort stage specific non coding rna expression patterns during in vitro human b cell differentiation into antibody secreting plasma cells
topic non-coding RNA
plasma cells
in vitro B cell differentiation
human B lymphocytes
RNA-seq
url https://www.mdpi.com/2311-553X/8/1/15
work_keys_str_mv AT reneectschumper stagespecificnoncodingrnaexpressionpatternsduringinvitrohumanbcelldifferentiationintoantibodysecretingplasmacells
AT dominiquebhoelzinger stagespecificnoncodingrnaexpressionpatternsduringinvitrohumanbcelldifferentiationintoantibodysecretingplasmacells
AT denisekwalters stagespecificnoncodingrnaexpressionpatternsduringinvitrohumanbcelldifferentiationintoantibodysecretingplasmacells
AT jaimeidavila stagespecificnoncodingrnaexpressionpatternsduringinvitrohumanbcelldifferentiationintoantibodysecretingplasmacells
AT collinaosborne stagespecificnoncodingrnaexpressionpatternsduringinvitrohumanbcelldifferentiationintoantibodysecretingplasmacells
AT dianefjelinek stagespecificnoncodingrnaexpressionpatternsduringinvitrohumanbcelldifferentiationintoantibodysecretingplasmacells