RNA-binding protein Ptbp1 is essential for BCR-mediated antibody production
| Autor: | Manabu Ozawa, Hiroki Sasanuma, Nobuaki Yoshida |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
T-Lymphocytes Immunology Receptors Antigen B-Cell Heterogeneous-Nuclear Ribonucleoproteins Antigen-Antibody Reactions Mice 03 medical and health sciences B-cell activation 0302 clinical medicine Immune system Antigen Gene expression medicine Animals Immunology and Allergy Immunodeficiency Original Research Mice Knockout B-Lymphocytes biology RBPs Alternative splicing breakpoint cluster region General Medicine PTBP1 medicine.disease Antigens T-Independent Molecular biology Mice Inbred C57BL 030104 developmental biology Antibody Formation biology.protein Antibody immunodeficiency Polypyrimidine Tract-Binding Protein 030215 immunology |
| Zdroj: | International Immunology |
| ISSN: | 1460-2377 |
| Popis: | B-cell Ptbp1 mediates normal antibody production The RNA-binding protein polypyrimidine tract-binding protein-1 (Ptbp1) binds to the pyrimidine-rich sequence of target RNA and controls gene expression via post-transcriptional regulation such as alternative splicing. Although Ptbp1 is highly expressed in B lymphocytes, its role to date is largely unknown. To clarify the role of Ptbp1 in B-cell development and function, we generated B-cell-specific Ptbp1-deficient (P1BKO) mice. B-cell development in the bone marrow, spleen and peritoneal cavity of the P1BKO mice was nearly normal. However, the P1BKO mice had significantly lower levels of natural antibodies in serum compared with those of the control mice. To investigate the effect of Ptbp1 deficiency on the immune response in vivo, we immunized the P1BKO mice with T-cell-independent type-2 (TI-2) antigen NP-Ficoll and T-cell-dependent (TD) antigen NP-CGG. We found that B-cell-specific Ptbp1 deficiency causes an immunodeficiency phenotype due to defective production of antibody against both TI-2 and TD antigen. This immunodeficiency was accompanied by impaired B-cell receptor (BCR)-mediated B-cell activation and plasmablast generation. These findings demonstrate that Ptbp1 is essential for the humoral immune response. |
| Databáze: | OpenAIRE |
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