TY - JOUR
T1 - VH replacement in mice and humans
AU - Zhang, Zhixin
N1 - Funding Information:
I am supported in part by a K01 grant AR048592 from NIH/NIAMS. I thank Max D. Cooper and Peter D. Burrows for critically reviewing this manuscript. I also thank Michael Zemlin and Torben Barington for many helpful discussions regarding the identification of potential V H replacement products.
PY - 2007/3
Y1 - 2007/3
N2 - Heavy chain variable segment (VH) replacement refers to recombination activating gene (RAG) product-mediated secondary recombination between a previously rearranged VH gene and an upstream unrearranged VH gene. VH 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 VH replacement intermediates during normal murine B cell development. In humans, ongoing VH replacement was found in a clonal B lineage EU12 cell line and in human bone marrow immature B cells. The identification of potential VH replacement products also suggested a potential contribution of VH replacement to the antibody repertoire. Here, I review the evidence for whether VH replacement genuinely offers an in vivo RAG-mediated recombinatorial mechanism to alter preformed IgH genes in mice and humans.
AB - Heavy chain variable segment (VH) replacement refers to recombination activating gene (RAG) product-mediated secondary recombination between a previously rearranged VH gene and an upstream unrearranged VH gene. VH 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 VH replacement intermediates during normal murine B cell development. In humans, ongoing VH replacement was found in a clonal B lineage EU12 cell line and in human bone marrow immature B cells. The identification of potential VH replacement products also suggested a potential contribution of VH replacement to the antibody repertoire. Here, I review the evidence for whether VH replacement genuinely offers an in vivo RAG-mediated recombinatorial mechanism to alter preformed IgH genes in mice and humans.
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U2 - 10.1016/j.it.2007.01.003
DO - 10.1016/j.it.2007.01.003
M3 - Review article
C2 - 17258935
AN - SCOPUS:33847160642
SN - 1471-4906
VL - 28
SP - 132
EP - 137
JO - Trends in Immunology
JF - Trends in Immunology
IS - 3
ER -