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在由靶基因对内源性H和kL链基因座抑制的背景下,作者研制出了“人类免疫球蛋白”,该球蛋白是由小鼠携带人H链(IgM)和K型(Igk)、λ型(Igλ)L链转基因座。转基因座的引进补充了小鼠脾脏中循环B细胞池存在的衰竭。这些小鼠的B淋巴细胞膜上表达了人IgM和Igk或Igλ蛋白质,携带的人Igλ基因座的显性性状大于k基因座。小鼠血清中分泌人IgM。在角疫作用之后,能产生特异性抗体反应。IgH重排时多样性和结合片段的作用和人B细胞非常相似。提示人细胸中通常直接重排的信使序列在小鼠B细胞中功能是完全的。另外,重排期间,片段之间加入了非模板‘N’核苷酸以增加多样性,在人B细胞中,同时存在H和L链,而转基因座小鼠只有H链。人Ig小鼠仅在H链上重排‘N’核苷酸,提示Ig转基因座重排在同发育阶段。在不同片段的启动基因序列中,由于可产生差异的V区基因的限制作用,H链似乎受到限制,这将影响重排期间“人免疫球蛋白”的活性。转基因小鼠重排的H链序列几乎没有由于种系不
In the context of inhibition of endogenous H and kL chain loci by target genes, the authors developed a “human immunoglobulin” that is a human immunoglobulin that carries human H chain (IgM) and K (Igk) , Lambda type (Ig lambda) L chain transposon. The introduction of the transgene locus complements the depletion of circulating B cell pools in the mouse spleen. These mice express human IgM and Igk or Igλ proteins on the membrane of B lymphocytes, carrying dominant human Igλ loci more than the k locus. Human serum secretes human IgM. After the role of Kok disease, can produce specific antibody response. The role of IgH rearrangement diversity and binding fragments is very similar to that of human B cells. Suggesting that the sequence of the messenger, which is usually directly rearranged in the human breast, is functional in mouse B cells. In addition, during rearrangement, non-template ’N’ nucleotides are added between the fragments to increase diversity, in human B cells, both H and L chains are present, whereas the transgenic mice have only H chains. Human Ig mice rearrange only the “N” nucleotides on the H chain, suggesting that Ig loci are rearranged in the same developmental stage. H chain seems to be limited in the promoter sequence of different fragments due to the restriction of V-region genes that can produce differences, which will affect the activity of “human immunoglobulins” during rearrangement. Almost no rearrangement of H chain sequences in transgenic mice due to germline no