@article{1aeabb631f704314b77b3a121946cac5,
title = "Defective B cell development and function in Btk-deficient mice",
abstract = "Mutations in the Bruton's tyrosine kinase (Btk) gene have been linked to severe early B cell developmental blocks in human X-linked agammaglobulinemia (XLA), and to milder B cell activation deficiencies in murine X-linked immune deficiency (Xid). To elucidate unequivocally potential Btk functions in mice, we generated mutations in embryonic stem cells, which eliminated the ability to encode Btk pleckstrin homology or kinase domains, and assayed their effects by RAG2-deficient blastocyst complementation or introduction into the germline. Both mutations block expression of Btk protein and lead to reduced numbers of mature conventional B cells, severe B1 cell deficiency, serum IgM and IgG3 deficiency, and defective responses in vitro to various B cell activators and in vivo to immunization with thymus-independent type II antigens. These results prove that lack of Btk function results in an Xid phenotype and further suggest a differential requirement for Btk during the early stages of murine versus human B lymphocyte development.",
author = "Khan, {Wasif N.} and Alt, {Frederick W.} and Gerstein, {Rachel M.} and Malynn, {Barbara A.} and Irene Larsson and Gary Rathbun and Laurie Davidson and Sussane M{\"u}ller and Kantor, {Aaron B.} and Herzenberg, {Leonora A.} and Rosen, {Fred S.} and Paschalis Sideras",
note = "Funding Information: Correspondence should be addressed to F. W. A. We thank Dr. H. Wortisfor CEA.xid/HHW miceand for helpful discussions; Dr. J. Kenny for C57BU6,xid mice; Dr. A. Abbas for advice and reagents for studies of the TD immune responses and for critical reading of the manuscript; Dr. A. Bottaro for helpful discussions regarding B cell activation assays; Dr. 0. Witte for anti-Btk antibodies; Dr. J. lnmann for TNP-Ficoll; and Dr. H. Kurasyama for IL-4 transfectants. We also thank G. Jager for excellent technical assistance and Dr. A. Stall for helpful discussions and critical reading of the manuscript. Ganciclovir is a generous gift of Syntex Corporation. This work was supported by the Howard Hughes Medical Institute and by National Institutes of Health grants A120047, POlAl35714, Al34762 to F. W. A. and LM04636 to L. A. H.; the Swedish Medical Research Council; and the Swedish CancerSociety(Cancerfonden)Grants B94-16X-1064501Aand 1619-B94-06XAC to P. S. and CA61009 B. A. M. R. G. is a fellow of the",
year = "1995",
month = sep,
doi = "10.1016/1074-7613(95)90114-0",
language = "English (US)",
volume = "3",
pages = "283--299",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "3",
}