Evidence for local expansion of IgA plasma cell precursors in human ileum
| Autor: | Frans G. M. Kroese, Nicolaas A. Bos, Maaike Stoel, Johannes G. M. Burgerhof, Saravanan Yuvaraj, Peter M. Dammers, Annie Visser, Gerard Dijkstra |
|---|---|
| Přispěvatelé: | Science in Healthy Ageing & healthcaRE (SHARE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Life Course Epidemiology (LCE), Groningen Institute for Organ Transplantation (GIOT) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
EXPRESSION
Pathology medicine.medical_specialty Somatic cell Biopsy Immunology Molecular Sequence Data Plasma Cells Immunoglobulin Variable Region Biology Plasma cell LAMINA PROPRIA Ileum Precursor cell medicine Immunology and Allergy Humans GUT Lamina propria medicine.diagnostic_test Base Sequence Precursor Cells B-Lymphoid Germinal center Molecular biology Immunoglobulin A LYMPHOID-TISSUE medicine.anatomical_structure Lymphatic system GERMINAL-CENTERS IMMUNOGLOBULIN biology.protein Somatic Hypermutation Immunoglobulin Antibody Immunoglobulin Heavy Chains ZONE B-CELLS Sequence Alignment REGION GENES GENERATION RESPONSES |
| Zdroj: | Journal of Immunology, 183(8), 4871-4878. AMER ASSOC IMMUNOLOGISTS |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | IgA plays a crucial role in establishment and maintenance of mucosal homeostasis between host cells and commensal bacteria. To this end, numerous IgA plasma cells are located in the intestinal lamina propria. Whether the (immediate) precursor cells for these plasma cells can expand locally is not completely known and was studied here. The total number of IgA plasma cells in human ileal biopsies was counted. Sequence analysis of IgA V(H) genes from human ileal biopsies revealed the occurrence of many clonally related sequences within a biopsy, but not between different biopsies. This observation strongly argues for local expansion of IgA precursor cells. By comparing the number of unique sequences with the number of clonally related sequences within a biopsy, we estimated that similar to 100-300 precursors were responsible for the 75,000 IgA-producing cells that were present per biopsy. These precursor cells must therefore have divided locally 9-10 times. Since all sequences contained mutations and most of the mutations present in clonally related sequences were shared, the IgA precursor cells must have arrived initially as mutated cells in the lamina propria. Our data show evidence for the existence of two waves of expansion for IgA-producing cells in human ileum. The first wave occurs during initial stimulation in germinal centers as evidenced by somatic hypermutations. A second wave of expansion of IgA-committed cells occurs locally within the lamina propria as evidenced by the high frequency of clonally related cells. The Journal of Immunology, 2009, 183: 4871-4878. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|