VH replacement in mice and humans.
Heavy chain variable segment (V(H)) replacement refers to recombination activating gene (RAG) product-mediated secondary recombination between a previously rearranged V(H) gene and an upstream unrearranged V(H) gene. V(H) replacement was first observed in mouse pre-B cell lines and later demonstrated in knock-in mouse models carrying immunoglobulin heavy chain (IgH) genes encoding self-reactive or mono-specific antibodies or non-functional IgH rearrangements on both IgH alleles. Despite these findings, it is still difficult to find V(H) replacement intermediates during normal murine B cell development. In humans, ongoing V(H) replacement was found in a clonal B lineage EU12 cell line and in human bone marrow immature B cells. The identification of potential V(H) replacement products also suggested a potential contribution of V(H) replacement to the antibody repertoire. Here, I review the evidence for whether V(H) replacement genuinely offers an in vivo RAG-mediated recombinatorial mechanism to alter preformed IgH genes in mice and humans.
Zhang
Zhixin
Z
Division of Developmental and Clinical Immunology, Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. zhixin.zhang@ccc.uab.edu
D000818:Animals; D000916:Antibody Diversity; D001402:B-Lymphocytes / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D009687:Nuclear Proteins / Q000502:physiology; D011995:Recombination, Genetic
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C064658:RAG-1 protein