Cbl-b differentially regulates activation-induced apoptosis in T helper 1 and T helper 2 cells.
We previously reported that ligation of CD3 induces antiapoptotic signals in T helper 2 (Th2) cells, and in contrast causes Th1 cells to undergo apoptosis. Here we show that Cbl-b is accountable for the unequal response, revealing a previously unknown cell-specific regulatory function for the molecule. Absence of Cbl-b resulted in resistance to activation-induced apoptosis in murine Th1 cells following CD3 ligation, akin to what is observed in Th2 cells containing Cbl-b. Concurrent with the apoptosis profile, CD3 ligation in the absence of Cbl-b induced raft mobilization and cytoskeletal rearrangement in Th1 cells. Despite their ability to signal from CD3, Th2 cells did not aggregate their rafts, providing an explanation for cell-specific activity of Cbl-b.
Hanlon
Allison
A
Temple University School of Medicine, Department of Microbiology and Immunology, Philadelphia, PA, USA.
Jang
Sihyug
S
Salgame
Padmini
P
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology*; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D005260:Female; D021962:Membrane Microdomains / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D050721:Proto-Oncogene Proteins c-cbl / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D017252:CD3 Complex; C118387:Cblb protein, mouse; D050721:Proto-Oncogene Proteins c-cbl