T Cell-Independent Somatic Hypermutation in Murine B Cells with an Immature Phenotype

Somatic hypermutation contributes to the generation of antibody diversity and is strongly associated with the maturation of antigen-specific immune responses. We asked whether somatic hypermutation also plays a role in the generation of the murine immunoglobulin repertoire during B cell development....

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Veröffentlicht in:Immunity (Cambridge, Mass.) Mass.), 2004-02, Vol.20 (2), p.133-144
Hauptverfasser: Mao, Changchuin, Jiang, Liying, Melo-Jorge, Milena, Puthenveetil, Maya, Zhang, Xiuli, Carroll, Michael C., Imanishi-Kari, Thereza
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container_end_page 144
container_issue 2
container_start_page 133
container_title Immunity (Cambridge, Mass.)
container_volume 20
creator Mao, Changchuin
Jiang, Liying
Melo-Jorge, Milena
Puthenveetil, Maya
Zhang, Xiuli
Carroll, Michael C.
Imanishi-Kari, Thereza
description Somatic hypermutation contributes to the generation of antibody diversity and is strongly associated with the maturation of antigen-specific immune responses. We asked whether somatic hypermutation also plays a role in the generation of the murine immunoglobulin repertoire during B cell development. To facilitate identification of somatic mutations, we examined mouse systems in which only antibodies expressing λ1, λ2, and λx light chains can be generated. Somatic mutations were found in cells, which, by surface markers, RAG expression, and rapid turnover, had the phenotype of immature B cells. In addition, expression of AID was detected in these cells. The mutations were limited to V regions and were localized in known hotspots. Mutation frequency was not diminished in the absence of T cells. Our results support the idea that somatic hypermutation can occur in murine immature B cells and may represent a mechanism for enlarging the V gene repertoire.
doi_str_mv 10.1016/S1074-7613(04)00019-6
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subjects activation-induced cytidine deaminase
Animals
B-Lymphocytes - cytology
B-Lymphocytes - physiology
Bone marrow
Bone Marrow Cells - immunology
Cell Differentiation
Cells, Cultured
Cytidine Deaminase - biosynthesis
DNA-Binding Proteins - biosynthesis
Flow Cytometry
Genes
Homeodomain Proteins - biosynthesis
Immune system
Immunoglobulin Variable Region - genetics
Mutation
Phenotype
Point Mutation
RAG gene
Reverse Transcriptase Polymerase Chain Reaction
somatic hypermutation
Somatic Hypermutation, Immunoglobulin - immunology
T-Lymphocytes - immunology
title T Cell-Independent Somatic Hypermutation in Murine B Cells with an Immature Phenotype
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