Loss of hnRNPLL‐dependent splicing of Ptprc has no impact on B‐cell development, activation and terminal differentiation into antibody‐secreting cells
| Autor: | Gerard F. Hoyne, Yavuz F Yazicioglu, Christopher C. Goodnow, Anselm Enders, Mehmet Yabas |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Heterogeneous nuclear ribonucleoprotein PTPRC Gene Plasma Cells Immunology PTPRC Heterogeneous-Nuclear Ribonucleoproteins Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Immunology and Allergy B cell B-Lymphocytes biology Alternative splicing Germinal center Cell Differentiation Cell Biology Natural killer T cell Phosphoric Monoester Hydrolases Cell biology 030104 developmental biology medicine.anatomical_structure RNA splicing biology.protein Leukocyte Common Antigens 030215 immunology |
| Zdroj: | Immunology & Cell Biology. 99:532-541 |
| ISSN: | 1440-1711 0818-9641 |
| DOI: | 10.1111/imcb.12433 |
| Popis: | 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 Hnrnpllthu/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, Hnrnpllthu/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 Hnrnpllthu/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. |
| Databáze: | OpenAIRE |
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