BCR Engagement Induces Fas Resistance in Primary B Cells in the Absence of Functional Bruton's Tyrosine Kinase

B cell susceptibility to Fas-mediated apoptosis is regulated in a receptor-specific fashion. CD40 engagement produces marked sensitivity to Fas killing, whereas surface Ig (sIg) engagement blocks Fas signaling for cell death in otherwise sensitive, CD40-stimulated B cell targets, and thus, induces a...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2002-03, Vol.168 (6), p.2712-2719
Main Authors: Tumang, Joseph R, Negm, Robert S, Solt, Laura A, Schneider, Thomas J, Colarusso, Thomas P, Hastings, William D, Woodland, Robert T, Rothstein, Thomas L
Format: Article
Language:English
Subjects:
Agammaglobulinaemia Tyrosine Kinase
Agammaglobulinemia - genetics
Agammaglobulinemia - immunology
Animals
Apoptosis - genetics
Apoptosis - immunology
B-Lymphocyte Subsets - enzymology
B-Lymphocyte Subsets - immunology
B-Lymphocyte Subsets - metabolism
Bruton's tyrosine kinase
CD40L protein
Fas antigen
fas Receptor - toxicity
Immunity, Innate - genetics
Male
Mice
Mice, Inbred A
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Knockout
Protein-Tyrosine Kinases - deficiency
Protein-Tyrosine Kinases - genetics
Protein-Tyrosine Kinases - physiology
Proto-Oncogene Proteins c-bcl-2 - biosynthesis
Receptors, Antigen, B-Cell - immunology
Receptors, Antigen, B-Cell - metabolism
Receptors, Antigen, B-Cell - physiology
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Summary:B cell susceptibility to Fas-mediated apoptosis is regulated in a receptor-specific fashion. CD40 engagement produces marked sensitivity to Fas killing, whereas surface Ig (sIg) engagement blocks Fas signaling for cell death in otherwise sensitive, CD40-stimulated B cell targets, and thus, induces a state of Fas resistance. The signaling mediator, Bruton's tyrosine kinase (Btk), is required for certain sIg-triggered responses, and Btk is reported to directly bind Fas and block Fas-mediated apoptosis. For these reasons, the role of Btk as a mediator of sIg-induced Fas resistance was examined. Dysfunction of Btk through mutation, and absence of Btk through deletion did not interfere with induction of Fas resistance by anti-Ig. This may be due, at least in part, to induction of Btk-dependent Bcl-2 family members by anti-Ig after CD40 ligand treatment. However, the susceptibility to Fas-mediated apoptosis of B cell targets stimulated by CD40 ligand alone was increased in the absence of Btk. These results indicate that Fas resistance produced by sIg triggering does not require Btk, but suggests that in certain situations Btk modulates B cell susceptibility to Fas killing.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.168.6.2712