@article{ee4a55db28884aa09c145f34861fb5dc,
title = "A class switch control region at the 3′ end of the immunoglobulin heavy chain locus",
abstract = "We replaced the IgH 3′ enhancer (3′EH) region with a neomycin resistance gene in ES cells and generated chimeric mice in which all mature lymphocytes were either heterozygous (3′EH+/-) or homozygous (3′EH-/-) for the mutation. In vitro activated 3′EH-/- B cells responded similarly to 3′EH+/- B cells with respect to proliferation and secretion of IgM and IgG1 but were specifically deficient in IgG2a, IgG2b, IgG3, and IgE secretion. These isotype deficiencies correlated with a deficiency in accumulation of transcripts from and class switching to affected CH genes. In vivo, chimeric mice containing only 3′EH-/- B cells were deficient in serum IgG2a and IgG3. We propose that the 3′EH-/- mutation disrupts the activity of a regulatory region that influences heavy chain class switching to several different CH genes that lie as far as 100 kb upstream of the mutation.",
author = "Michel Cogn{\'e} and Rusty Lansford and Andrea Bottaro and Jue Zhang and James Gorman and Faith Young and Cheng, {Hwel Ling} and Alt, {Frederick W.}",
note = "Funding Information: Michel Cogni,{\textquoteleft}t* Rusty Lansford,{\textquoteleft}* Andrea Bottaro,{\textquoteleft}§t Jue Zhang; Faith Young,{\textquoteright} Hwei-Ling Cheng,{\textquoteright} {\textquoteleft}and Frederick W. Ah{\textquoteright} {\textquoteleft}The Howard Hughes Medical Institute The Children{\textquoteright}s Hospital The Center for Blood Research and Department of Genetics Harvard Medical School Boston, Massachusetts 02115 tlnstitut de Biologie Moleculaire et dlngenierie Genetique Unite de Recherche Associee Centre National de la Recherche Scientifique Faculte des Sciences F-86022 Poitiers France SDipartimento di Biologia Molecolare Universita di Siena Policlinico Le Scotte 53100 Siena Italy Funding Information: We thank Suzanne Li for the IgH 3{\textquoteright} enhancer probe and for probes used in Sl experiments, Ms. Deborah Ahern for advice in FACScan analyses, Dr. Robert Coffman (DNAX, Palo Alto, California) for rewm-binant IL-4 and advice on ELISA assays, Drs. T. Hirano and K. Oku-mura (Juntendo University, Tokyo, Japan) for anti-IgE antibodies, Val-erie Stewart and Laurie Davidson for assistance with blastocyst injections and mouse work, and Mark Groudine for critically reading this manuscript This work was supported by the Howard Hughes Medical Institute and National Institutes of Health grants Al-20047 and Al-31541 (to F. W. A.). M. C. was supported by a grant from the Centre National de la Recherche Scientifique, the National Institutes of Health, and the North AtlanticTreaty Organization, A. B. by a European Molecular Biology Organization fellowship, and J. G. by a Life and Health Insurance Medical Research Fund Fellowship.",
year = "1994",
month = jun,
day = "3",
doi = "10.1016/0092-8674(94)90057-4",
language = "English (US)",
volume = "77",
pages = "737--747",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "5",
}