Flexible ordering of antibody class switch and V(D)J joining during B-cell ontogeny

Omenn syndrome is a severe immunodeficiency disease commonly arising from hypomorphic RAG recombinase gene mutations. RAG recombinase mediates V(D)J joining during early B-lymphocyte development in the bone marrow (BM). V(D)J recombination and class switch recombination are thought to partition between the BM and secondary lymphoid organs. Kenter and colleagues show that V(D)J joining and switching are interchangeably inducible in the BM. This study has important implications for the development of Omenn syndrome, autoimmune diseases, and leukemia.

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