Human fetal, cord blood, and adult lymphocyte progenitors have similar potential for generating B cells with a diverse immunoglobulin repertoire
| Autor: | Maria Isabel D. Rossi, Grant R. Kolar, Takafumi Yokota, J. Donald Capra, Swapan K. Nath |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Lymphocyte Transplantation Heterologous Immunology Immunoglobulins Bone Marrow Cells Immunoglobulin E Biochemistry Mice Fetus Immune system medicine Animals Humans Regeneration Lymphopoiesis Aged Aged 80 and over Mice Knockout Genetics B-Lymphocytes Transplantation Chimera Base Sequence biology Repertoire Age Factors Hematopoietic Stem Cell Transplantation Cell Biology Hematology Fetal Blood Hematopoietic Stem Cells medicine.anatomical_structure Cord blood Antibody Formation biology.protein Immunoglobulin heavy chain Antibody Immunoglobulin Heavy Chains |
| Zdroj: | Blood. 104:2981-2987 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2003-11-3961 |
| Popis: | Several characteristics of the immunoglobulin (Ig) repertoire in fetuses and adults set them apart from each other. Functionally, this translates into differences in the affinity and effectiveness of the humoral immune response between adults and the very young. At least 2 possibilities could explain these differences: (1) fetal and adult lymphocyte progenitors differ significantly in their potential to form a diverse repertoire, and (2) factors extrinsic to the immunoglobulin locus are more influential to the character of the repertoire. To address this we used nonobese diabetic-severe combined immunodeficient-β2 microglobulin knockout (NOD/SCID/β2m-/-) mice reconstituted with human B-cell progenitors to compare the immunoglobulin repertoire potential of human fetal, cord blood, and adult sources. We found nearly identical VH and JH gene segment use and only modest differences in the third complementarity determining region of the immunoglobulin heavy chain (HCDR3). We conclude that the repertoire potential is remarkably similar regardless of the age of the individual from which progenitors are derived. Age-related differences in the immunoglobulin repertoire and variance of B-cell responses to immunization appear to arise from selection rather than from changes in recombination of the immunoglobulin locus itself. From the standpoint of the Ig repertoire, an immune system reconstituted from fetal or neonatal stem cells would likely be as diverse as one generated from adult bone marrow. |
| Databáze: | OpenAIRE |
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