TY - JOUR
T1 - An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells
AU - Salerno, Fiamma
AU - Howden, Andrew J. M.
AU - Matheson, Louise S.
AU - Gizlenci, Özge
AU - Screen, Michael
AU - Lingel, Holger
AU - Brunner-Weinzierl, Monika C.
AU - Turner, Martin
N1 - Funding Information:
We thank Doreen Cantrell for support and the Biological Support Unit, Next Generation Sequencing, Flow Cytometry and Bioinformatics facilities of the Babraham Institute, the Mass Spectrometry facility of University of Dundee, and the Next Generation Sequencing of the CRUK for outstanding technical assistance. We thank Simon Andrews, Claudia Ribeiro de Almeida and Sarah E. Bell for critical review of the manuscript, and Sarah Collinson for formatting the Supplementary Figure File. This study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) (BBS/E/B/000C0427; BBS/E/B/000C0428), the BBSRC Core Capability Grant to the Babraham Institute, the H2020-Marie Skłodowska-Curie Innovative Training Network 765158 “COSMIC” and a Wellcome Investigator award (200823/Z/16/Z). F.S. was supported by European Molecular Biology Organization (EMBO) Long-Term Fellowship (ALTF 880-2018) and H2020-Marie Skłodowska-Curie Individual Fellowship (841930, B-different). M.C.B.W. was supported by Deutsche Forschungsgemeinschaft (DFG) SFB854 B14 and Br1860/12.
Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/8/23
Y1 - 2023/8/23
N2 - During B cell maturation, transitional and mature B cells acquire cell-intrinsic features that determine their ability to exit quiescence and mount effective immune responses. Here we use label-free proteomics to quantify the proteome of B cell subsets from the mouse spleen and map the differential expression of environmental sensing, transcription, and translation initiation factors that define cellular identity and function. Cross-examination of the full-length transcriptome and proteome identifies mRNAs related to B cell activation and antibody secretion that are not accompanied by detection of the encoded proteins. In addition, proteomic data further suggests that the translational repressor PDCD4 restrains B cell responses, in particular those from marginal zone B cells, to a T-cell independent antigen. In summary, our molecular characterization of B cell maturation presents a valuable resource to further explore the mechanisms underpinning the specialized functions of B cell subsets, and suggest the presence of 'poised' mRNAs that enable expedited B cell responses.
AB - During B cell maturation, transitional and mature B cells acquire cell-intrinsic features that determine their ability to exit quiescence and mount effective immune responses. Here we use label-free proteomics to quantify the proteome of B cell subsets from the mouse spleen and map the differential expression of environmental sensing, transcription, and translation initiation factors that define cellular identity and function. Cross-examination of the full-length transcriptome and proteome identifies mRNAs related to B cell activation and antibody secretion that are not accompanied by detection of the encoded proteins. In addition, proteomic data further suggests that the translational repressor PDCD4 restrains B cell responses, in particular those from marginal zone B cells, to a T-cell independent antigen. In summary, our molecular characterization of B cell maturation presents a valuable resource to further explore the mechanisms underpinning the specialized functions of B cell subsets, and suggest the presence of 'poised' mRNAs that enable expedited B cell responses.
KW - B-Lymphocytes/cytology
KW - Proteome
KW - Transcriptome
KW - Animals
KW - Mice
KW - Cell Differentiation
KW - Transcription Factors/metabolism
KW - RNA, Messenger
KW - Protein Biosynthesis
KW - B-Lymphocyte Subsets/metabolism
UR - http://www.scopus.com/inward/record.url?scp=85168565181&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-40621-2
DO - 10.1038/s41467-023-40621-2
M3 - Article
C2 - 37612319
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
M1 - 5116
ER -