IMMUNOGLOBULIN STRUCTURE & DIVERSITY--CHARACTERIZATION OF CELL MEMBRANE PROTEINS

(1)已经建立了一个SCID小鼠集落，以检查在体内方面， 肿瘤和正常发育。首先，该系统 用于分析浆细胞瘤的基本遗传要求 诱导SCID小鼠已经用来自以下任一种的骨髓重建： 敏感或耐药菌株，并已进行肿瘤诱导 确定遗传背景相对贡献的方案 与诱导过程中潜在的B细胞缺陷相比。SCID模型是 也被用来评估各种正常的遗传潜力， 通过适当的重建实验确定淋巴细胞群。（二） 浆细胞瘤的最初发展一直难以研究， 不能在培养物中生长早期肿瘤或阻止它们生长， 发展到后期的表型。这个问题现在已经 显著减少的能力，证明增长的主要 在由自体粘附细胞组成的饲养层上的体外浆细胞瘤 来自同一肿瘤的细胞。这些馈线的特性， 目前正在评价它们与浆细胞瘤细胞的相互作用。 (3)两项长期的基因研究，调节分化的基因， 造血干细胞还在继续。在第一个系统中， 事件数量，包括GM-CSF和IL-6的产生，下调 fos和fms mRNA转录上调， CD45亚型表达可能有助于向髓样转化 通过双能B淋巴细胞祖细胞分化。详细研究 B淋巴细胞和髓系细胞发育过程中CD 45亚型表达的变化 细胞已经启动。对lpr或gld纯合子小鼠的进一步研究， 干扰正常T细胞分化和功能的基因， 显示在TcR交联后，扩增的DN T细胞 不能产生一系列的淋巴因子，而稀释的CD4 + T细胞过度产生参与炎症反应的淋巴因子， 从而可能导致自身免疫性疾病的发展。

(1) A SCID mouse colony has been established to examine in vivo aspects of both neoplastic and normal development. In the first instance, this system is being used to analyze the basic genetic requirements for plasmacytoma induction. SCID mice have been reconstituted with bone marrow from either susceptible or resistant strains and have been subjected to tumor induction protocols to determine the relative contributions of genetic background versus potential B-cell defects in the induction process. The SCID model is also being used to assess the genetic potential of various normal lymphocyte populations through appropriate reconstitution experiments. (2) The initial development of plasmacytomas has been difficult to study due to the inability to grow early stage tumors in culture or prevent them from progressing to later stage phenotypes. This problem has now been significantly lessened by the demonstrated ability to grow primary plasmacytomas in vitro on feeder layers consisting of autologous adherent cells derived from the same tumor. Characterization of these feeders and their interactions with plasmacytoma cells are currently being evaluated. (3) Two longstanding studies of genes that regulate the differentiation of hematopoietic cells have continued. In the first system it was shown that a number of events including production of GM-CSF and IL-6, down regulation of myb and up regulation of fos and fms mRNA transcripts and changes in CD45 isoform expression may contribute to the switch to myeloid differentiation by bipotential B lymphocyte progenitors. A detailed study of CD45 isoform expression during development of B lymphocytes and myeloid cells was initiated. Further studies of mice homozygous for lpr or gld, two genes that interfere with normal T cell differentiation and function, showed that following cross linking of the TcR, the expanded DN T cells were unable to produce a spectrum of lymphokines, whereas the diluted CD4+ T cells overproduced lymphokines involved in inflammatory responses and thus may contribute to the development of autoimmune disease.