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| [PMID]: | 28760881 |
| [Au] Autor: | Iacoangeli A; Lui A; Haines A; Ohta Y; Flajnik M; Hsu E |
| [Ad] Endereço: | Tisch Multiple Sclerosis Research Center of New York, New York, NY 10019. |
| [Ti] Título: | Evidence for Ig Light Chain Isotype Exclusion in Shark B Lymphocytes Suggests Ordered Mechanisms. |
| [So] Source: | J Immunol;199(5):1875-1885, 2017 Sep 01. | | [Is] ISSN: | 1550-6606 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | Unlike most vertebrates, the shark IgL gene organization precludes secondary rearrangements that delete self-reactive VJ rearranged genes. Nurse sharks express four L chain isotypes, κ, λ, σ, and σ-2, encoded by 35 functional minigenes or clusters. The sequence of gene activation/expression and receptor editing of these isotypes have not been studied. We therefore investigated the extent of isotypic exclusion in separated B cell subpopulations. Surface Ig (sIg)κ-expressing cells, isolated with mAb LK14 that recognizes Cκ, carry predominantly nonproductive rearrangements of other L chain isotypes. Conversely, after depletion with LK14, sIgM cells contained largely nonproductive κ and enrichment for in-frame VJ of the others. Because some isotypic inclusion was observed at the mRNA level, expression in the BCR was examined. Functional λ mRNA was obtained, as expected, from the LK14-depleted population, but was also in sIgκ splenocytes. Whereas λ somatic mutants from the depleted sample displayed evidence of positive selection, the λ genes in sIgκ cells accumulated bystander mutations indicating a failure to express their products at the cell surface in association with the BCR H chain. In conclusion, a shark B cell expresses one L chain isotype at the surface and other isotypes as nonproductive VJ, sterile transcripts, or in-frame VJ whose products may not associate with the H chain. Based on the mRNA content found in the B cell subpopulations, an order of L chain gene activation is suggested as: σ-2 followed by κ, then σ and λ. |
| [Mh] Termos MeSH primário: |
Subpopulações de Linfócitos B/fisiologia
Linfócitos B/fisiologia
Proteínas de Peixes/genética
Rearranjo Gênico de Cadeia Leve de Linfócito B
Isotipos de Imunoglobulinas/genética
Cadeias Leves de Imunoglobulina/genética
Receptores de Antígenos de Linfócitos B/genética
Tubarões/imunologia
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| [Mh] Termos MeSH secundário: |
Animais
Células Cultivadas
Feminino
Regulação da Expressão Gênica
Loci Gênicos
Estruturas Genéticas
Switching de Imunoglobulina
Masculino
RNA Mensageiro
Vertebrados
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| [Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Fish Proteins); 0 (Immunoglobulin Isotypes); 0 (Immunoglobulin Light Chains); 0 (RNA, Messenger); 0 (Receptors, Antigen, B-Cell) |
| [Em] Mês de entrada: | 1709 |
| [Cu] Atualização por classe: | 170929 |
[Lr] Data última revisão:
| 170929 |
| [Sb] Subgrupo de revista: | AIM; IM |
| [Da] Data de entrada para processamento: | 170802 |
| [St] Status: | MEDLINE |
| [do] DOI: | 10.4049/jimmunol.1700762 |
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