The V lambda J lambda repertoire in human fetal spleen: evidence for positive selection and extensive receptor editing
| Autor: | J, Lee, N L, Monson, P E, Lipsky |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adult
Genes Immunoglobulin Molecular Sequence Data B-Lymphocyte Subsets Immunoglobulin Variable Region Receptors Antigen B-Cell Complementarity Determining Regions Fetus Immunoglobulin M Immunoglobulin lambda-Chains Immunoglobulin J-Chains Multigene Family Humans RNA Editing Gene Rearrangement B-Lymphocyte Spleen Antibody Diversity |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 165(11) |
| ISSN: | 0022-1767 |
| Popis: | VlambdaJlambda rearrangements obtained from genomic DNA of individual IgM(+) B cells from human fetal spleen were analyzed. A nonrandom pattern of lambda gene rearrangements that differed from the adult Vlambda repertoire was found. The Vlambda distal genes 8A and 4B were absent from the nonproductive fetal repertoire, whereas 2E and 3L were overrepresented and 1B was underrepresented in the productive fetal repertoire. Positive selection of the Vlambda gene, 2E, along with Vlambda rearrangements employing homologous VlambdaJlambda joins were observed in the fetal, but not in the adult Vlambda repertoire. Overrepresentation of Jlambda distal cluster C genes rearranging to the Vlambda distal J segment, Jlambda7, in both productive and nonproductive fetal repertoires suggested that receptor editing/replacement was more active in the fetus than in adults. Numerous identical VlambdaJlambda junctions were observed in both the productive and nonproductive repertoire of the fetus and adult, but were significantly more frequent in the productive repertoire of the fetus, suggesting expansion of B cells expressing particular lambda-light chains in both stages of development, with more profound expansion in the fetal repertoire. Notably, B cells expressing identical lambda-light chains expressed diverse heavy chains. These data demonstrate that three mechanisms strongly influence the shaping of the human fetal lambda-chain repertoire that are less evident in the adult: positive selection, receptor editing, and expansion of B cells expressing specific lambda-light chains. These events imply that the expressed fetal repertoire is shaped by exposure to self Ags. |
| Databáze: | OpenAIRE |
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