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

IG遗传学--兔免疫系统细胞的个体发育和分化

• 批准号: 3768720
• 负责人: R G MAGE
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3768720
• 关键词: B lymphocyte; cell differentiation; gene expression; gene rearrangement; gut associated lymphoid tissue; immunoglobulin genes; immunoglobulins; laboratory rabbit; lectin; leukopoiesis; nucleic acid sequence

We use techniques of immunogenetics and of molecular biology to study the rabbit immunoglobulins (Igs), and related genes such as the recombination activating genes RAG-1 and RAG-2 which are necessary for gene rearrangements to occur during lymphocyte development. We investigate the development of anatomical sites such as appendix follicles and germinal centers in gut associated lymphoid tissues and the regulated expression and sequence diversification of Ig genes during lymphoid cell development. Membrane IgD has not been definitively identified on rabbit B cells; the genetic region which should contain the delta gene has been cloned, but sequences corresponding to delta heavy chain exons have not been identified. We have identified two surface immunoglobulin complexes on rabbit peripheral blood B cells that possess heavy chains of similar apparent molecular size confirming previous reports of the presence of a second surface receptor expressed on rabbit B cells which may be IgD or an IgM-related molecule. In noncovalent association with one or both of these receptors are several proteins that are components of surface immunoglobulin (mIg) complexes expressed on rabbit B cells. Three proteins (42 kDa, 37kDa, 36kDa) were found in association with IgM expressed on B cells from peripheral blood and spleen. These proteins may be the rabbit homologues of murine Ig-beta (B29), Ig-gamma (truncated B29) and Ig-alpha (mb-1). Lectins are allowing us to dissect rabbit appendix follicles and germinal centers into subcompartments based on local expression of glycosylated cell surface receptors. We found two additional IgM-associated protein complexes containing 36kDa and 34kDa proteins in lysates from individual follicles isolated from the appendix. The appendix may be functioning early in development like the chicken bursa or sheep ileal Peyer's patch. However, the rabbit appendix does not involute but may alter its function and become a secondary lymphoid organ in the adult.

我们使用免疫遗传学和分子生物学技术来研究 兔免疫球蛋白（Ig）和相关基因，如重组 激活基因RAG-1和RAG-2是基因表达所必需的， 在淋巴细胞发育过程中发生重排。我们调查的 阑尾滤泡和生殖器等解剖部位的发育 肠相关淋巴组织中的中心和调节表达 和淋巴细胞发育过程中IG基因序列的多样化。 在兔B细胞上尚未明确鉴定出膜IgD; 应该包含delta基因的基因区域已经被克隆，但是 对应于δ重链外显子的序列尚未被 鉴定 我们已经确定了两个表面免疫球蛋白复合物上 具有类似重链的兔外周血B细胞 表观分子大小证实了先前关于存在 在兔B细胞上表达的第二表面受体，其可以是IgD或 IgM相关分子。 与以下一种或两种非共价缔合 这些受体是几种蛋白质， 在兔B细胞上表达的免疫球蛋白（mIg）复合物。 三 与IgM结合的蛋白质为42 kDa、37 kDa、36 kDa 在来自外周血和脾的B细胞上表达。 这些蛋白质可能 是鼠Ig-β（B29）、Ig-γ（截短的B29）的兔同源物 和Ig-α（mb-1）。 凝集素使我们能够解剖兔子的阑尾 毛囊和生殖器中心到亚隔室的基础上，当地 糖基化细胞表面受体的表达。我们发现了另外两个 IgM相关蛋白复合物，含有36kDa和34kDa蛋白， 从阑尾分离的单个卵泡的裂解物。 的 阑尾可能在发育早期起作用，如鸡的法氏囊或 绵羊回肠派伊尔集合淋巴结。 然而，兔阑尾并不内卷 但也可能改变其功能，成为淋巴细胞中的次级淋巴器官。 成年人了