Chen Liguang, Apgar John, Huynh Lang, Dicker Frank, Giago-McGahan Teresa, Rassenti Laura, Weiss Arthur, Kipps Thomas J
Division of Hematology/Oncology, Department of Medicine, University of California, San Diego, 9500 Gilman Dr, UCSD School of Medicine, La Jolla, CA 92093, USA.
Blood. 2005 Mar 1;105(5):2036-41. doi: 10.1182/blood-2004-05-1715. Epub 2004 Oct 28.
Chronic lymphocytic leukemia (CLL) B cells that express unmutated immunoglobulin heavy-chain variable region genes (IgV(H)) generally express ZAP-70, in contrast to normal B cells or most CLL cases with mutated IgV(H). Following IgM ligation, ZAP-70+ CLL cells had significantly higher levels of phosphorylated p72(Syk), BLNK, and phospholipase-Cgamma (PLCgamma) and had greater[Ca2+]i flux than did ZAP-70-negative CLL cases, including unusual ZAP-70-negative cases with unmutated IgV(H). IgM ligation of ZAP-70-negative CLL B cells infected with an adenovirus vector encoding ZAP-70 induced significantly greater levels of phosphorylated p72(Syk), BLNK, and PLCgamma and had greater[Ca2+]i flux than did similarly stimulated, noninfected CLL cells or CLL cells infected with a control adenovirus vector. We conclude that expression of ZAP-70 in CLL allows for more effective IgM signaling in CLL B cells, a feature that could contribute to the relatively aggressive clinical behavior generally associated with CLL cells that express unmutated IgV(H).
与正常B细胞或大多数免疫球蛋白重链可变区基因（IgV(H)）发生突变的慢性淋巴细胞白血病（CLL）病例不同，表达未突变IgV(H)的CLL B细胞通常表达ZAP-70。在IgM连接后，ZAP-70阳性的CLL细胞中磷酸化p72(Syk)、BLNK和磷脂酶Cγ（PLCγ）的水平显著更高，并且与ZAP-70阴性的CLL病例（包括IgV(H)未突变的罕见ZAP-70阴性病例）相比，其[Ca2+]i通量更大。用编码ZAP-70的腺病毒载体感染的ZAP-70阴性CLL B细胞进行IgM连接，与同样受到刺激的未感染CLL细胞或感染对照腺病毒载体的CLL细胞相比，诱导的磷酸化p72(Syk)、BLNK和PLCγ水平显著更高，且[Ca2+]i通量更大。我们得出结论，CLL中ZAP-70的表达使CLL B细胞中的IgM信号传导更有效，这一特征可能导致通常与表达未突变IgV(H)的CLL细胞相关的相对侵袭性临床行为。
