Independent and opposing roles for Btk and lyn in B and myeloid signaling pathways

Anne B. Satterthwaite, Clifford A. Lowell, Wasif Khan, Paschalis Sideras, Frederick W. Alt, Owen N. Witte

Research output: Contribution to journalArticle

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Abstract

Transphosphorylation by Src family kinases is required for the activation of Bruton's tyrosine kinase (Btk). Differences in the phenotypes of Btk(-/-) and lyn(-/-) mice suggest that these kinases may also have independent or opposing functions. B cell development and function were examined in Btk(-/-)lyn(-/-) mice to better understand the functional interaction of Btk and Lyn in vivo. The antigen-independent phase of B lymphopoiesis was normal in Btk(-/-)lyn(-/-) mice. However, Btk(-/-)lyn(-/-) animals had a more severe immunodeficiency than Btk(-/-) mice B cell numbers and response to T cell-dependent antigens were reduced. Btk and Lyn therefore play independent or partially redundant roles in the maintenance and function of peripheral B cells. Autoimmunity, hypersensitivity to B cell receptor (BCR) cross-linking, and splenomegaly caused by myeloerythroid hyperplasia were alleviated by Btk deficiency in lyn(-/-) mice. A transgene expressing Btk at ~25% of endogenous levels (Btk(lo)) was crossed onto Btk(-/-) and Btk(-/-)lyn(-/-) backgrounds to demonstrate that Btk is limiting for BCR. signaling in the presence but not in the absence of Lyn. These observations indicate that the net outcome of Lyn function in vivo is to inhibit Btk- dependent pathways in B and myeloid cells, and that Btk(lo) mice are a useful sensitized system to identify regulatory components of Btk signaling pathways.

Original languageEnglish
Pages (from-to)833-844
Number of pages12
JournalJournal of Experimental Medicine
Volume188
Issue number5
DOIs
StatePublished - Sep 7 1998
Externally publishedYes

Fingerprint

B-Lymphocytes
Agammaglobulinaemia tyrosine kinase
Lymphopoiesis
Antigens
src-Family Kinases
Splenomegaly
Myeloid Cells
Autoimmunity
Transgenes
Hyperplasia
Hypersensitivity
Phosphotransferases
Cell Count
Maintenance
T-Lymphocytes
Phenotype

Keywords

  • B cell development
  • B cell receptor
  • Immunodeficiency
  • Src family kinases
  • Transgenic mice

ASJC Scopus subject areas

  • Immunology

Cite this

Independent and opposing roles for Btk and lyn in B and myeloid signaling pathways. / Satterthwaite, Anne B.; Lowell, Clifford A.; Khan, Wasif; Sideras, Paschalis; Alt, Frederick W.; Witte, Owen N.

In: Journal of Experimental Medicine, Vol. 188, No. 5, 07.09.1998, p. 833-844.

Research output: Contribution to journalArticle

Satterthwaite, Anne B. ; Lowell, Clifford A. ; Khan, Wasif ; Sideras, Paschalis ; Alt, Frederick W. ; Witte, Owen N. / Independent and opposing roles for Btk and lyn in B and myeloid signaling pathways. In: Journal of Experimental Medicine. 1998 ; Vol. 188, No. 5. pp. 833-844.
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