Xid Affects Events Leading to B Cell Cycle Entry

Kurt Brorson*, Mark Brunswick, Sergei Ezhevsky, Datsen George Wei, Ryan Berg, David Scott, Kathryn E. Stein

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


X-linked agammaglobulinemia patients and X-linked immunodeficient (xid) mice possess mutations in the Bruton's tyrosine kinase (Btk kinase) gene and display defects in B cell development and activation by slg cross-linking. Btk is an early activation kinase in slg-cross-linked B cells, xid does not ablate Btk protein kinase activity, and immediate signal transduction events, such as tyrosine phosphorylation, occur in slg-activated xid B cells. These cells do not subsequently progress into cell division and have a high rate of apoptosis, which has been shown to correlate with an absence of slg-mediated induction of the bcl-xL protein. To establish the point where Btk activity is critical for progression beyond immediate signaling, we examined early and late events in slg-cross-linked xid B cells. Induction of proto-oncogenes and nuclear factors occurred normally in xid cells. However, induction of cyclins and increased GAPDH mRNA was not observed in xid cells. Degradation of the cyclin inhibitor p27 Kip1. occurred normally in xid cells. After 24 h of culture with anti-μ, the remaining live, nonapoptotic xid cells were enlarged, viable, and primed for subsequent stimulation by LPS. Our data suggest that the Btk kinase is not essential for several G1 events and that the failure of slg-activated xid B cells to enter cell cycle correlates with a defect of cyclin induction. Moreover, these data suggest that Btk is important not only for immediate events following B cell activation and control of apoptosis but also for subsequent events leading to cyclin activation.

Original languageEnglish
Pages (from-to)135-143
Number of pages9
JournalJournal of Immunology
Issue number1
StatePublished - 1997
Externally publishedYes


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