Unimpaired Activation of c-Jun NH_2-Terminal Kinase (JNK) 1 upon CD40 Stimulation in B Cells of Patients with X-Linked Agammaglobulinemia

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• 作者：Brunner ; Cornelia ; Kreth ; Hans Wolfgang ; Ochs ; Hans D. ; Schuster ; Volker
• 关键词：Btk ; XLA ; CD40 ; JNK ; EBV
• 刊名：Journal of Clinical Immunology
• 出版年：2002
• 出版时间：2002
• 年：2002
• 卷：22
• 期：4
• 页码：244-251
• 全文大小：851 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Immunology
  Infectious Diseases
  Internal Medicine
  Medical Microbiology
  
• 出版者：Springer Netherlands
• ISSN：1573-2592

文摘

X-linked agammaglobulinemia (XLA) is caused by mutations in the gene encoding the cytoplasmic Bruton’s tyrosine kinase (Btk). Btk has been shown to play an essential role in the development of B1 (CD5$^+$) and conventional circulating mature B cells (B2) in mouse and man. It has been shown in earlier studies that Btk is involved in both the BCR- and CD40-mediated signaling pathways. In this study, we analyzed the responsiveness of Epstein-Barr virus (EBV) transformed B cells from nine XLA patients to CD40 stimulation, particularly the CD40 induced activation of c-Jun N-terminal kinase (JNK). In eight XLA patients the JNK activation was unimpaired and in one case JNK could not be activated by anti-CD40 stimulation. Btk protein expression was detectable by Western blotting in six cases, in one case Btk expression was drastically reduced, and in three cases no Btk expression could be observed. Btk kinase activity was found in three cases and it was reduced in one and not detectable in five cases. Furthermore, in one female patient with an agammaglobulinemia, Btk expression and function as well as JNK activation by CD40 stimulation was unimpaired. Our findings demonstrate that JNK activation via the CD40 signaling pathway is intact in EBV-transformed B cells of most if not all XLA patients, independent of the mutation and its effect on Btk expression and kinase activity. We suggest that Btk is not necessary for the activation of JNK upon CD40 stimulation, at least in the B cell subpopulation we had studied. We cannot exclude that these B cells belong to a “leaky” B-cell subpopulation in which the CD40 signaling pathway has become independent of Btk function.