Loss of hnRNPLL-dependent splicing of Ptprc has no impact on B-cell development, activation and terminal differentiation into antibody-secreting cells

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dc.authoridYabas, Mehmet/0000-0002-3462-5389
dc.authoridEnders, Anselm/0000-0001-5933-6463
dc.authoridHoyne, Gerard/0000-0002-7370-9139
dc.authoridYazicioglu, Yavuz/0000-0003-3731-9333
dc.authorwosidYabas, Mehmet/D-9513-2012
dc.authorwosidEnders, Anselm/B-1165-2011
dc.authorwosidHoyne, Gerard/M-5406-2013
dc.contributor.authorYabas, Mehmet
dc.contributor.authorYazicioglu, Yavuz F.
dc.contributor.authorHoyne, Gerard F.
dc.contributor.authorGoodnow, Christopher C.
dc.contributor.authorEnders, Anselm
dc.date.accessioned2024-06-12T10:51:20Z
dc.date.available2024-06-12T10:51:20Z
dc.date.issued2021
dc.departmentTrakya Üniversitesien_US
dc.description.abstractThe RNA-binding protein heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) controls alternative splicing of protein tyrosine phosphatase receptor type C (Ptprc) which encodes CD45. hnRNPLL deficiency leads to a failure in silencing Ptprc exons 4-6 causing aberrant expression of the corresponding CD45 isoforms, namely, CD45RA, RB and RC. While an N-ethyl-N-nitrosourea-induced point mutation in murine Hnrnpll results in loss of peripheral naive T cells, its role in B-cell biology remains unclear. Here, we demonstrate that B-cell development in the bone marrow of Hnrnpll(thu/thu) mice is normal and the number of mature B-cell subsets in the spleen and peritoneal cavity is comparable to control littermates. In response to in vivo immunization, Hnrnpll(thu/thu) mice were deficient in generating germinal center (GC) B cells, and analysis of mixed bone marrow chimeras revealed that the GC B-cell deficiency was a B-cell extrinsic effect of the hnRNPLL mutation. Mature Hnrnpll(thu/thu) B cells proliferated normally in response to various B-cell receptor- and Toll-like receptor-mediated stimuli. Similarly, in vitro stimulation of mutant B cells led to normal generation of plasmablasts, but mutant plasmablasts failed to downregulate B220 expression because of the inability of cells to undergo proper CD45 pre-messenger RNA alternative splicing. These findings collectively suggest that, like in T and natural killer T cells, the mutation disrupts hnRNPLL-mediated alternative splicing of the Ptprc gene in plasmablasts, but this dysregulation of Ptprc alternative splicing does not affect the development and function of B cells.en_US
dc.description.sponsorshipNHMRC Career Development Fellowship; Ramaciotti Foundationen_US
dc.description.sponsorshipAE was supported by an NHMRC Career Development Fellowship and by the Ramaciotti Foundation. We thank the staff of the Australian Phenomics Facility for animal husbandry, DNA preparation and genotyping; the staff of the Imaging and Cytometry Facility at the John Curtin School of Medical Research for help with flow cytometry; Mrs Debbie Howard for help with bone marrow chimera experiments and Ms Clara Young for help with nitrophenyl-Ficoll immunization. We also thank Dr Lisa Miosge for critical reading of the manuscript.en_US
dc.identifier.doi10.1111/imcb.12433
dc.identifier.endpage541en_US
dc.identifier.issn0818-9641
dc.identifier.issn1440-1711
dc.identifier.issue5en_US
dc.identifier.pmid33331104en_US
dc.identifier.scopus2-s2.0-85100045837en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage532en_US
dc.identifier.urihttps://doi.org/10.1111/imcb.12433
dc.identifier.urihttps://hdl.handle.net/20.500.14551/18324
dc.identifier.volume99en_US
dc.identifier.wosWOS:000613188900001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofImmunology And Cell Biologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAlternative Splicingen_US
dc.subjectB Cellsen_US
dc.subjectCD45en_US
dc.subjectHnrnpllen_US
dc.subjectImmunologyen_US
dc.subjectPlasma Cellsen_US
dc.titleLoss of hnRNPLL-dependent splicing of Ptprc has no impact on B-cell development, activation and terminal differentiation into antibody-secreting cellsen_US
dc.typeArticleen_US

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