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Loss of hnRNPLL‐dependent splicing of Ptprc has no impact on B‐cell development, activation and terminal differentiation into antibody‐secreting cells
Author(s) -
Yabas Mehmet,
Yazicioglu Yavuz F,
Hoyne Gerard F,
Goodnow Christopher C,
Enders Anselm
Publication year - 2021
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12433
Subject(s) - biology , germinal center , alternative splicing , b cell , protein tyrosine phosphatase , microbiology and biotechnology , rna splicing , cancer research , immunology , exon , antibody , signal transduction , rna , genetics , gene
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 naïve 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.