Programs in Systems Biology; Department of Biochemistry and Molecular Pharmacology
Developmental Biology | Genetics and Genomics | Systems Biology
V(D)J joining is mediated by RAG recombinase during early B-lymphocyte development in the bone marrow (BM). Activation-induced deaminase initiates isotype switching in mature B cells of secondary lymphoid structures. Previous studies questioned the strict ontological partitioning of these processes. We show that pro-B cells undergo robust switching to a subset of immunoglobulin H (IgH) isotypes. Chromatin studies reveal that in pro-B cells, the spatial organization of the Igh locus may restrict switching to this subset of isotypes. We demonstrate that in the BM, V(D)J joining and switching are interchangeably inducible, providing an explanation for the hyper-IgE phenotype of Omenn syndrome.
B-cell development, Ag gene rearrangement, Gene expression
DOI of Published Version
Kumar S, Wuerffel R, Achour I, Lajoie B, Sen R, Dekker J, Feeney AJ, Kenter AL. Flexible ordering of antibody class switch and V(D)J joining during B-cell ontogeny. Genes Dev. 2013 Nov 15;27(22):2439-44. doi: 10.1101/gad.227165.113. Link to article on publisher's site
Genes and development
Kumar, Satyendra; Wuerffel, Robert; Achour, Ikbel; Lajoie, Bryan R.; Sen, Ranjan; Dekker, Job; Feeney, Ann J.; and Kenter, Amy L., "Flexible ordering of antibody class switch and V(D)J joining during B-cell ontogeny" (2013). Program in Systems Biology Publications and Presentations. 37.