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

• Published in: Immunity (Cambridge, Mass.) Vol. 20; no. 2; pp. 133 - 144
• Main Authors: Mao, Changchuin, Jiang, Liying, Melo-Jorge, Milena, Puthenveetil, Maya, Zhang, Xiuli, Carroll, Michael C., Imanishi-Kari, Thereza
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2004; Elsevier Limited
• 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
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(04)00019-6

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.