DOI: 10.1073/pnas.94.24.13152. Btk dosage determines sensitivity to B cell antigen receptor cross-linking

Btk dosage determines sensitivity to B cell antigen receptor cross-linking

10.1073/pnas.94.24.13152

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Mutations in Btk result in the B cell immunodeficiencies X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Btk is a critical component of signaling pathways regulating B cell development and function. We used a genetic approach to determine whether Btk is also limiting for these processes. 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–Ficoll response, anti-IgM-induced proliferation, B1 cell development, and serum IgM and IgG3levels remained significantly impaired in these animals. B cells from Btk −/− 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–Ficoll 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.

Bibliography

Satterthwaite, A. B., Cheroutre, H., Khan, W. N., Sideras, P., & Witte, O. N. (1997). Btk dosage determines sensitivity to B cell antigen receptorâcross-linking. Proceedings of the National Academy of Sciences, 94(24), 13152â13157.

Authors 5

Anne B. Satterthwaite (first)
Hilde Cheroutre (additional)
Wasif N. Khan (additional)
Pascalis Sideras (additional)
Owen N. Witte (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:32 a.m.)
Deposited	2 years, 4 months ago (April 22, 2023, 8:11 a.m.)
Indexed	1 week, 1 day ago (Aug. 24, 2025, 6:50 p.m.)
Issued	27 years, 9 months ago (Nov. 25, 1997)
Published	27 years, 9 months ago (Nov. 25, 1997)
Published Online	27 years, 9 months ago (Nov. 25, 1997)
Published Print	27 years, 9 months ago (Nov. 25, 1997)

Funders 0

None

BibTeX

@article{Satterthwaite_1997, title={Btk dosage determines sensitivity to B cell antigen receptor cross-linking}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.24.13152}, DOI={10.1073/pnas.94.24.13152}, number={24}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Satterthwaite, Anne B. and Cheroutre, Hilde and Khan, Wasif N. and Sideras, Pascalis and Witte, Owen N.}, year={1997}, month=nov, pages={13152–13157} }

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