دورية أكاديمية
The Ig heavy chain protein but not its message controls early B cell development.
| العنوان: | The Ig heavy chain protein but not its message controls early B cell development. |
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| المؤلفون: | Aslam MA; Division of Tumor Biology and Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.; Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, 60800 Multan, Pakistan., Alemdehy MF; Division of Tumor Biology and Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands., Hao B; Department of Pathology, New York University School of Medicine, New York, NY 10016., Krijger PHL; Hubrecht Institute-Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands., Pritchard CEJ; Mouse Clinic for Cancer and Aging Transgenic Facility, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands., de Rink I; Genome Core Facility, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands., Muhaimin FI; Division of Tumor Biology and Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands., Nurzijah I; Division of Tumor Biology and Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands., van Baalen M; Flow Cytometry Facility, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands., Kerkhoven RM; Genome Core Facility, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands., van den Berk PCM; Division of Tumor Biology and Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands., Skok JA; Department of Pathology, New York University School of Medicine, New York, NY 10016., Jacobs H; Division of Tumor Biology and Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; h.jacobs@nki.nl. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Dec 08; Vol. 117 (49), pp. 31343-31352. Date of Electronic Publication: 2020 Nov 23. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | B-Lymphocytes/*cytology , B-Lymphocytes/*metabolism , Immunoglobulin Heavy Chains/*genetics , Immunoglobulin Heavy Chains/*metabolism, Alleles ; Animals ; Biomarkers/metabolism ; Genetic Loci ; Mice, Inbred C57BL ; Precursor Cells, B-Lymphoid/cytology ; Precursor Cells, B-Lymphoid/immunology ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Reproducibility of Results |
| مستخلص: | Development of progenitor B cells (ProB cells) into precursor B cells (PreB cells) is dictated by immunoglobulin heavy chain checkpoint (IgHCC), where the IgHC encoded by a productively rearranged Igh allele assembles into a PreB cell receptor complex (PreBCR) to generate signals to initiate this transition and suppressing antigen receptor gene recombination, ensuring that only one productive Igh allele is expressed, a phenomenon known as Igh allelic exclusion. In contrast to a productively rearranged Igh allele, the Igh messenger RNA (mRNA) ( IgHR ) from a nonproductively rearranged Igh allele is degraded by nonsense-mediated decay (NMD). This fact prohibited firm conclusions regarding the contribution of stable IgHR to the molecular and developmental changes associated with the IgHCC. This point was addressed by generating the Igh Ter5H∆TM mouse model from Igh Ter5H mice having a premature termination codon at position +5 in leader exon of Igh Ter5H allele. This prohibited NMD, and the lack of a transmembrane region (∆TM) prevented the formation of any signaling-competent PreBCR complexes that may arise as a result of read-through translation across premature Ter5 stop codon. A highly sensitive sandwich Western blot revealed read-through translation of Igh Ter5H message, indicating that previous conclusions regarding a role of IgHR in establishing allelic exclusion requires further exploration. As determined by RNA sequencing (RNA-Seq), this low amount of IgHC sufficed to initiate PreB cell markers normally associated with PreBCR signaling. In contrast, the Igh Ter5H∆TM knock-in allele, which generated stable IgHR but no detectable IgHC, failed to induce PreB development. Our data indicate that the IgHCC is controlled at the level of IgHC and not IgHR expression. Competing Interests: The authors declare no competing interest. (Copyright © 2020 the Author(s). Published by PNAS.) |
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| معلومات مُعتمدة: | R35 GM122515 United States GM NIGMS NIH HHS |
| فهرسة مساهمة: | Keywords: Ig heavy chain checkpoint; PreB cell antigen receptor; allelic exclusion; early B cell development; read-through translation |
| المشرفين على المادة: | 0 (Biomarkers) 0 (Immunoglobulin Heavy Chains) 0 (RNA, Messenger) |
| تواريخ الأحداث: | Date Created: 20201124 Date Completed: 20210121 Latest Revision: 20240804 |
| رمز التحديث: | 20240804 |
| مُعرف محوري في PubMed: | PMC7733823 |
| DOI: | 10.1073/pnas.2004810117 |
| PMID: | 33229554 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
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| DOI: | 10.1073/pnas.2004810117 |