Apoptosis induced by the antigen receptor and Fas in a variant of the immature B cell line WEHI-231 and in splenic immature B cells

• Published in: International immunology Vol. 13; no. 4; pp. 581 - 592
• Main Authors: Tian, Maoxin Tim, Chou, Chih-Hao Gilbert, DeFranco, Anthony L.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.04.2001; Oxford Publishing Limited (England)
• Subjects: Animals; Apoptosis; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; BCR; BD BOC-Asp-FMK; CD40 antigen; CD40 Antigens - immunology; CD40 Antigens - metabolism; Cell Cycle; Cell Line; Clone Cells - immunology; DEVD Z-Asp-Glu-Val-Asp-FMK; Dose-Response Relationship, Immunologic; Fas; Fas antigen; fas Receptor - immunology; fas Receptor - metabolism; growth arrest; immature B lymphocytes; JNK Jun N-terminal kinase; LEHD Z-Leu-Glu-His-Asp-FMK; Mice; Mice, Inbred BALB C; PARP poly(ADP-ribose) polymerase; PI propidium iodide; Receptors, Antigen, B-Cell - immunology; Receptors, Antigen, B-Cell - metabolism; Signal Transduction; Spleen - immunology; TNF tumor necrosis factor; TNFR tumor necrosis factor receptor; VAD Z-Val-Ala-Asp-FMK
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/13.4.581

Signaling by the BCR causes proliferation and resistance to Fas-induced apoptosis in mature B cells, but growth arrest and apoptosis in immature B cells. We have identified a variant of the immature B cell line WEHI 231 that retains the apoptotic response to the BCR but has acquired susceptibility to Fas-induced apoptosis. The Fas susceptibility was associated with increased Fas expression on the cell surface and down-regulated IgD expression. These cells exhibited a distinctive functional relationship in response to signals from the BCR, Fas and CD40: BCR stimulation markedly promoted Fas-mediated apoptosis (and vice versa) and Fas-induced apoptosis was not subject to modulation by CD40 signaling. While BCR-induced apoptosis was effectively rescued by CD40, it was not affected by the expression of a dominant-negative FADD. The mechanistic distinctions between BCR- and Fas-induced apoptosis were further characterized by the differential effects of different caspase inhibitors on these two processes which imply the involvement of different subsets of caspases. For BCR-induced apoptosis, we provide evidence that the final apoptotic destruction phase can be inhibited by the pan-caspase inhibitor BOC-Asp-FMK (BD) and that, in the presence of BD, the BCR only induces growth arrest which is reversible. The striking enhancing effects of Fas on BCR-induced apoptosis seen in the variant cells prompted us to examine if a similar cooperation in induction of apoptosis occurs in the highly tolerizable immature B cells of the spleen. We found that the splenic immature B population contains a significant number of Fas-expressing cells, but neither Fas-induced apoptosis nor an enhancing effect of Fas on BCR-induced apoptosis of these cells was detected in vitro.