A1 expression is stimulated by CD40 in B cells and rescues WEHI 231 cells from anti‐IgM‐induced cell death

• Published in: European journal of immunology 1999-10, Vol.29 (10), p.3077-3088
• Main Authors: Kuss, Andreas W., Knödel, Matthias, Berberich‐Siebelt, Friederike, Lindemann, Dirk, Schimpl, Anneliese, Berberich, Ingolf
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Anti-Idiotypic - immunology; Apoptosis; Apoptosis - immunology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; bcl‐2; CD40 Antigens - immunology; Cell Cycle - immunology; Cell Division - immunology; Cell Survival - immunology; DNA Fragmentation - immunology; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - physiology; Growth arrest; Homeodomain Proteins; Immature B cell; Immunoglobulin M - immunology; Lymphoma, B-Cell; Maturation; Mice; Minor Histocompatibility Antigens; Proto-Oncogene Proteins c-bcl-2 - immunology; Replication Protein C; Repressor Proteins; RNA, Messenger - biosynthesis; Saccharomyces cerevisiae Proteins; Tumor Cells, Cultured
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/(SICI)1521-4141(199910)29:10<3077::AID-IMMU3077>3.0.CO;2-R

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. Consistant 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.