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One allele of a murine Btk transgene expressed a dosage of Btk (25% of endogenous levels in splenic B cells) sufficient to restore normal numbers of phenotypically mature conventional B cells in xid mice. 2,4,6-trinitrophenyl\u2013Ficoll response, anti-IgM-induced proliferation, B1 cell development, and serum IgM and IgG\n                    <jats:sub>3<\/jats:sub>\n                    levels remained significantly impaired in these animals. B cells from Btk \u2212\/\u2212 transgenic mice also responded poorly to anti-IgM, indicating that the xid mutation does not create a dominant negative form of Btk. Response to 2,4,6-trinitrophenyl\u2013Ficoll and B cell receptor cross-linking were increased 3- to 4-fold in xid mice homozygous for the transgene. These results demonstrate that Btk is a limiting component of B cell antigen receptor signaling pathways and suggest that B cell development and response to antigen may require different levels of Btk activity.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.24.13152","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:32:33Z","timestamp":1027679553000},"page":"13152-13157","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":76,"title":["Btk dosage determines sensitivity to B cell antigen receptor\u2009cross-linking"],"prefix":"10.1073","volume":"94","author":[{"given":"Anne B.","family":"Satterthwaite","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Howard Hughes Medical Institute, and Department of Microbiology and Immunology, University of California, Los Angeles, CA 90095; Howard Hughes Medical Institute, The Children\u2019s Hospital, 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