IMMUNOGLOBULIN STRUCTURE & DIVERSITY--CHARACTERIZATION OF CELL MEMBRANE PROTEINS

I.与淋巴细胞发育异常有关的问题正在 在迈克尔·波特博士开发的浆细胞瘤模型中接近。 浆细胞瘤诱导的一个基本观察结果是， BALB/c品系高度敏感，而DBA/2等其它品系高度敏感， 抵抗 我们已经通过以下方法研究了DBA/2抗性的生物学基础： 将BALB/c或DBA/2骨引入一系列转移实验， 骨髓移植到SCID小鼠中，随后进行肿瘤诱导方案。 肿瘤 引产采用经典的降植烷治疗或使用 逆转录病毒构建体，J3V1，提供失调的myc和raf癌基因。 这些研究表明，用BALB/c骨重建的SCID小鼠 骨髓并注射J3V1的小鼠发生浆细胞瘤和骨髓肿瘤。 相比之下，DBA/2重建的SCID仅发生髓系肿瘤， 这表明两种菌株之间的遗传差异， 浆细胞瘤诱导，驻留在DBA/2 B细胞， 通过引入去调节的myc不能克服耐药性 在BALB/c中，该癌基因似乎是诱导的关键。 二.的 另外还使用SCID小鼠研究正常淋巴细胞 分化 我们最初用派尔氏菌重组了SCID 斑片细胞作为在一个专门的细胞中发现的群体的代表 粘膜免疫系统的组成部分。 重建的SCID小鼠具有 在6个月的时间内进行分析，以确定血清和 组织轮廓 重组小鼠显示血清免疫球蛋白 在定性和定量方面与正常动物相似 尽管Peyer集合淋巴结B细胞仅表达IgM和IgA。 所有淋巴组织，包括粘膜表面（肠、肺）、外周 器官（脾、淋巴结）和胸腺被重建。 正常 解剖结构如脾和淋巴结生发中心， 在组织切片中容易可见。 胸腺组织显示正常 解剖区域（皮质和髓质），但再生是由成熟， 单阳性（CD4）或（CD8）T细胞。 这些研究的结果有 器官特异性淋巴细胞归巢模型的重要意义， 以及分化过程中细胞定型的概念。

I. Questions related to abnormal lymphocyte development are being approached in the plasmacytoma model developed by Dr. Michael Potter. One of the basic observations of plasmacytoma induction is that the BALB/c strain is highly susceptible, but others, including DBA/2, are resistant. We have examined the biological basis for DBA/2 resistance by a series of transfer experiments introducing either BALB/c or DBA/2 bone marrow into SCID mice followed by tumor induction protocols. Tumor induction has employed either classic pristane treatment or the use of a retroviral construct, J3Vl, supplying deregulated myc and raf oncogenes. These studies indicate that SCID mice reconstituted with BALB/c bone marrow and injected with J3Vl develop plasmacytomas and myeloid tumors. In contrast, DBA/2 reconstituted SCIDs develop only myeloid tumors indicating that the genetic difference between the two strains, in terms of plasmacytoma induction, resides in the DBA/2 B-cell and that resistance cannot be overcome by the introduction of a deregulated myc oncogene which seems to be critical for induction in BALB/c. II. The SCID mouse has additionally been used to study normal lymphocyte differentiation. We have initially reconstituted SCIDs with Peyer's patch cells as representatives of populations found in a specialized component of the mucosal immune system. Reconstituted SCID mice have been analyzed over a period of 6 months to establish both serum and tissue profiles. Reconstituted mice display a serum immunoglobulin profile similar to normal animals both qualitatively and quantitatively in spite of the fact that Peyer's patch B cells express only IgM and IgA. All lymphoid tissues including mucosal surfaces (gut, lungs), peripheral organs (spleen, lymph nodes) and the thymus are reconstituted. Normal anatomical structures such as spleen and lymph node germinal centers are readily visible in tissue sections. Thymic tissue reveals normal anatomical areas (cortex and medulla), but repopulation is by mature, single positive (CD4) or (CD8) T cells. Results of these studies have important implications for models of organ specific lymphocyte homing as well as concepts of cellular commitment during differentiation.