Publications
Loss of hnRNPLL-dependent splicing of Ptprc has no impact on B-cell development, activation and terminal differentiation into antibody-secreting cells
Abstract
The 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.
Type | Journal |
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ISBN | 1440-1711 (Electronic) 0818-9641 (Linking) |
Authors | Yabas, M.; Yazicioglu, Y. F.; Hoyne, G. F.; Goodnow, C. C.; Enders, A. |
Responsible Garvan Author | Professor Christopher Goodnow |
Publisher Name | IMMUNOLOGY AND CELL BIOLOGY |
Published Date | 2021-05-31 |
Published Volume | 99 |
Published Issue | 5 |
Published Pages | 532-541 |
Status | Published in-print |
DOI | 10.1111/imcb.12433 |
URL link to publisher's version | https://www.ncbi.nlm.nih.gov/pubmed/33331104 |