Selection of individual VH genes occurs at the pro-B to pre-B cell transition
| Autor: | Philip L. Cohen, Emily Xue, Avinash Maganty, Martin Weigert, Eline T. Luning Prak, Lenka Yunk, Wenzhao Meng, Li-San Wang, Stéphane Mancini, Robert A. Eisenberg |
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| Přispěvatelé: | University of Pennsylvania - Department of Pathology & Laboratory Medecine, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Temple University School of Medecine - Section of Rheumatology, University of Pennsylvania - Division of Rheumatology, University of Chicago - Gwen Knapp Center for Lupus & Immonology Research, University of Chicago, University of Chicago - Department of Pathology/Molecular Pathogenesis & Molecular Medecine, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania-University of Pennsylvania |
| Rok vydání: | 2011 |
| Předmět: |
MESH: Somatic Hypermutation
Immunoglobulin Immunology Cell Somatic hypermutation Complementarity determining region Biology CDR3 Spectratyping Article 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine medicine Immunology and Allergy Animals MESH: Animals Gene MESH: Mice B cell 030304 developmental biology Genetics 0303 health sciences Transition (genetics) Precursor Cells B-Lymphoid MESH: DNA DNA Molecular biology MESH: Gene Expression Regulation Complementarity Determining Regions medicine.anatomical_structure chemistry Gene Expression Regulation MESH: Precursor Cells B-Lymphoid Proto-Oncogene Proteins c-bcr MESH: Complementarity Determining Regions [SDV.IMM]Life Sciences [q-bio]/Immunology Somatic Hypermutation Immunoglobulin MESH: Proto-Oncogene Proteins c-bcr 030215 immunology |
| Zdroj: | Journal of Immunology Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2011, 187 (4), pp.1835-44. ⟨10.4049/jimmunol.1100207⟩ Journal of Immunology, 2011, 187 (4), pp.1835-44. ⟨10.4049/jimmunol.1100207⟩ |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1100207⟩ |
| Popis: | B cells are subjected to selection at multiple checkpoints during their development. The selection of Ab H chains is difficult to study because of the large diversity of the CDR3. To study the selection of individual Ab H chain V region genes (VH), we performed CDR3 spectratyping of ∼75–300 rearrangements per individual VH in C57BL6/J mice. We measured the fraction of rearrangements that were in-frame in B cell DNA. We demonstrate that individual VHs have different fractions of in-frame rearrangements (IF fractions) ranging from 10 to 90% and that these IF fractions are reproducible in different mice. For most VHs, the IF fraction in pro-B cells approximated 33% and then shifted to the nearly final (mature) B cell value by the cycling pre-B cell stage. The frequency of high in-frame (IF) VH usage increased in cycling pre-B cells compared with that in pro-B cells, whereas this did not occur for low IF VHs. The IF fraction did not shift as much in BCR-expressing B cells and was minimally affected by L chain usage for most VH. High IF clan II/III VHs share more positively charged CDR2 sequences, whereas high IF clan I J558 CDR2 sequences are diverse. These data indicate that individual VHs are subjected to differential selection, that VH IF fraction is mainly established through pre-BCR–mediated selection, that it may operate differently in clan I versus II/III VHs, and that it has a lasting influence on the Ab repertoire. |
| Databáze: | OpenAIRE |
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