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  • Title: A1 expression is stimulated by CD40 in B cells and rescues WEHI 231 cells from anti-IgM-induced cell death.
    Author: Kuss AW, Knödel M, Berberich-Siebelt F, Lindemann D, Schimpl A, Berberich I.
    Journal: Eur J Immunol; 1999 Oct; 29(10):3077-88. PubMed ID: 10540318.
    Abstract:
    Engagement of the antigen receptor on murine immature B cells leads to growth arrest followed by apoptosis. Concomitant signaling through CD40 sustains proliferation and rescues the cells from apoptosis. We show here that cross-linking CD40 stimulates the expression of A1, a member of the anti-apoptotic Bcl-2 family, in primary murine B lymphocytes. CD40-dependent stimulation of A1 was confirmed in WEHI 231 cells, an immature murine B cell lymphoma line. We transduced WEHI 231 cells with a bicistronic recombinant retroviral vector coding for A1 and a chimeric selection marker comprising the enhanced yellow fluorescent protein and the zeocin resistance protein. A1-transduced WEHI 231 cells showed a significant higher survival rate after engagement of the antigen receptor. In contrast, constitutive expression of A1 did not abrogate anti-IgM-induced c-myc down-regulation. Consistent with this, A1 did not release anti-IgM-induced cell cycle arrest. Our data indicate that CD40-stimulated A1 expression permits WEHI 231 cells to survive in the presence of anti-IgM antibodies and suggests a protective role for A1 in antigen receptor-mediated apoptosis in B cells.
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