Role of tumor-associated, phosphorylated glycoprotein-membrane-antigen in bovine leukemia virus-induced lymphosarcoma.

牛白血病病毒（BLV）与牛地方性白血病（EBL）有关，EBL是牛最常见的肿瘤性疾病。为了阐明BLV感染的牛从无症状阶段进展到淋巴瘤阶段的方式，我们生产了一种单克隆抗体（Mab）c143，该抗体可识别在BLV感染的B淋巴细胞转化状态下磷酸化的肿瘤相关抗原（TAA）。在无BLV的正常牛中，TAA主要在B细胞、巨噬细胞、网状细胞和少量BoCD 4阳性T细胞上表达。由于c143 TAA的性质很可能是主要组织相容性复合体（MHC）II类抗原，我们分离了牛MHC（BoLA）α链（36-37 kD）和β链（32和34 kD）的cDNA，产生了表达单一类型BoLA II类分子的转染子，并用c143 Mab通过流式细胞术对其进行了分析。c143单抗识别表达BoLA-DR的转染细胞，但不识别BoLA-DQ，而c143单抗或抗BoLA-DR单抗处理淋巴细胞则产生不同的效应。尽管加入抗BoLA-DR单抗可抑制混合淋巴细胞反应（MLR），但c143单抗并不抑制MLR中T细胞的增殖反应，在健康人中，c143单抗可引起淋巴细胞自发增殖反应的增加，而抗BoLA-DR单抗则无此作用，且携带者淋巴细胞的自发增殖反应更强。此外，BLV感染绵羊中c143 Mab的免疫组织化学染色模式与抗BoLA-DR Mab的免疫组织化学染色模式存在显着差异。以c143 Mab作为肿瘤标记物鉴定EBL的免疫组织化学检查表明，牛白血病病毒转化的淋巴细胞或肿瘤细胞外周血中最早期聚集在边缘窦区，随后增殖并浸润到滤泡中，导致淋巴肉瘤的临床症状的发展。

Bovine leukemia virus (BLV) is associated with enzootic bovine leukosis (EBL), which is the most common neoplastic disease of cattle. To clarify the way in which BLV-infected cattle progress from the asymptomatic stage to the lymphoma stage, we produced a monoclonal antibody (Mab) c143 which recognized a tumor-associated antigen (TAA) that is phosphorylated in the transformed state of BLV-infected B-lymphoid cells. The TAA was mainly expressed on B-cells, macrophages, reticular cells, and a minor population of BoCD4-positive T-cells in BLV-free normal cattle. Since the nature of c143 TAA was likely to be that of the major histocompatibility complex (MHC) class II antigens, we isolated cDNAs for bovine MHC (BoLA) class alpha-chains (36-37 kD) and beta-chains (32 and 34 kD), produced transfectants that expressed a single type of BoLA class II molecules and analyzed them by flow cytometry with c143 Mab. The c143 Mab recognized the transfectant expressing BoLA-DR but not BoLA-DQ.However, the treatment of lymphocytes with c143 or anti-BoLA-DR Mab induced different effects. Although mixed lymphocyte reaction (MLR) was inhibited by the addition of anti-BoLA-DR Mab, the c143 Mab did not inhibit a proliferative response of T cells in MLR.Increased spontaneous proliferation of lymphocytes in healthy donors was obtained in the presence of c143 Mab but not anti-BoLA-DR Mab, and was much in lymphocytes from the carrier. More over, the patterns of immunohistological staining for c143 Mab in BLV-infected sheep showed distinguishing differences from those of anti-BoLA-DR Mabs.An immunohistochemical examination using c143 Mab as tumor marker for identification of EBL indicated that the bovine leukemia virus-transformed lymphocytes or neoplastic cells in peripheral blood accumulate in the marginal sinus area at the earliest stages, and subsequently proliferate and infiltrate into follicles, leading to the development of clinical signs of lymphosarcoma.