Flexible ordering of antibody class switch and V(D)J joining during B-cell ontogeny.
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.
Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, Illinois 60612, USA;
Satyendra
S
Kumar
Robert
R
Wuerffel
Ikbel
I
Achour
Bryan
B
Lajoie
Ranjan
R
Sen
Job
J
Dekker
Ann J
AJ
Feeney
Amy L
AL
Kenter
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D007132:Immunoglobulin Isotypes / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000378:metabolism; D050441:VDJ Exons / Q000502:physiology*
D007132:Immunoglobulin Isotypes
Ag gene rearrangement; B-cell development; gene expression