Kuss A W, Knödel M, Berberich-Siebelt F, Lindemann D, Schimpl A, Berberich I
Institute of Virology and Immunology, University of Würzburg, Würzburg, Germany.
Eur J Immunol. 1999 Oct;29(10):3077-88. 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. 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.
鼠未成熟B细胞上抗原受体的激活会导致生长停滞，随后发生凋亡。通过CD40的伴随信号传导可维持细胞增殖并使细胞免于凋亡。我们在此表明，交联CD40可刺激原代鼠B淋巴细胞中抗凋亡Bcl-2家族成员A1的表达。在未成熟鼠B细胞淋巴瘤系WEHI 231细胞中证实了CD40依赖性对A1的刺激。我们用编码A1和包含增强型黄色荧光蛋白及博来霉素抗性蛋白的嵌合选择标记的双顺反子重组逆转录病毒载体转导WEHI 231细胞。抗原受体激活后，转导A1的WEHI 231细胞显示出显著更高的存活率。相反，A1的组成型表达并未消除抗IgM诱导的c-myc下调。与此一致，A1并未解除抗IgM诱导的细胞周期停滞。我们的数据表明，CD40刺激的A1表达使WEHI 231细胞在抗IgM抗体存在的情况下存活，并提示A1在B细胞抗原受体介导的凋亡中具有保护作用。
