IG GENETICS--ONTOGENY AND DIFFERENTIATION OF CELLS OF THE RABBIT IMMUNE SYSTEM

我们使用经典的免疫遗传学和分子生物学技术， 研究兔免疫球蛋白（Ig）、T细胞受体 (Tcr)以及相关基因如重组酶激活基因RAG-1 和RAG-2，这是必要的基因重排发生在 淋巴细胞发育我们调查了老年中心的发展 以及IG基因的调控表达和序列多样性 在淋巴细胞发育过程中。 四个VH-CH重组位点图3 ' VH基因的5 ′端和JH基因的5 ′端。似乎有两个或更多 “重组热点”在重复DNA片段内或附近， 兔子的含DH区域。第五种重组体（R7K）具有 定位编码IgM膜末端的外显子3 '的位点 重链（Cmu）和C γ的5 ′。 这种重组的确切位置 以及其可能定位于与 其他物种含有IgD重链的外显子，目前正在 调查 与大多数研究的哺乳动物相反，膜-IgD没有 在兔B细胞上被明确鉴定。 我们已经确定了两个 兔外周血B细胞表面免疫球蛋白复合物， 具有相似表观分子大小的重链。 这些可以 代表与兔IgM和IgD的复合物。 发现了四种蛋白质 与每个受体中的mIg非共价结合。这些 包括42、37和36 kD蛋白，它们可能是 鼠Ig-β（B29）和Ig-γ和Ig-α（mb-1）。这些蛋白质 发现与75 kD和115 kD异聚复合物相关。 两个较大 糖蛋白（100和150 kD）可能特异性地与 非μ受体。 Ig相关蛋白在B淋巴细胞中变化 分离自脾脏、血液、骨髓和肠道相关淋巴 组织（GALT）。 凝集素使我们能够将兔子的GALT分解成 基于细胞局部累积的子区室， 特别是低聚糖。 正常和VH表达突变的兔 显示出相似的染色模式;导致 不同VH基因组的表达似乎不影响 GALT的总体架构。

We use techniques of classical immunogenetics and of molecular biology to study the genetics of rabbit immunoglobulins (Igs ), T cell receptors (Tcr), and related genes such as the recombinase activating genes RAG-1 and RAG-2 which are necessary for gene rearrangements to occur during lymphocyte development. We investigate the development of germinal centers and the regulated expression and sequence diversification of Ig genes during lymphoid cell development. Four VH-CH recombination sites map 3' of the VH genes and 5' of the JH genes. There appear to be two or more "hot-spots of recombination" within or near stretches of repetitive DNA in the DH-containing region of the rabbit. A fifth recombinant (R7K) has a site that maps 3' of the exons encoding the membrane terminus of the IgM heavy chain (Cmu) and 5' of Cgamma. The exact site of this recombination and its possible localization in a region homologous to the region in other species containing exons for the IgD heavy chain is currently under investigation. In contrast to most mammals studied, membrane-IgD has not been definitively identified on rabbit B cells. We have identified two surface immunoglobulin complexes on rabbit peripheral blood B cells that possess heavy chains of similar apparent molecular size. These may represent complexes with rabbit IgM and IgD. Four proteins are found noncovalently associated with the mIg in each of the receptors. These include 42, 37 and 36 kD proteins that may be the rabbit homologues of murine Ig-beta (B29) and Ig-gamma and Ig-alpha (mb-1). These proteins are found associated as 75 kd and 115 kD heteromeric complexes. Two larger glycoproteins (100 and 150 kD) may be specifically associated with the non-mu receptor. The Ig-associated proteins vary in B-lymphocytes isolated from spleen, blood, bone marrow and gut associated lymphoid tissue (GALT). Lectins are allowing us to dissect rabbit GALT into subcompartments based on local accumulations of cells expressing particular oligosaccharides. Normal and VH-expression mutant ali rabbits show similar staining patterns;the defect in ali rabbits which leads to the expression of a different set of VH genes does not appear to affect the general architecture of GALT.