Sayegh C E, Demaries S L, Iacampo S, Ratcliffe M J
Department of Microbiology and Immunology, McGill University, 3775 University Street, Montreal, QC, Canada H3A 2B4.
Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10806-11. doi: 10.1073/pnas.96.19.10806.
Immunoglobulin gene rearrangement in avian B cell precursors generates surface Ig receptors of limited diversity. It has been proposed that specificities encoded by these receptors play a critical role in B lineage development by recognizing endogenous ligands within the bursa of Fabricius. To address this issue directly we have introduced a truncated surface IgM, lacking variable region domains, into developing B precursors by retroviral gene transfer in vivo. Cells expressing this truncated receptor lack endogenous surface IgM, and the low level of endogenous Ig rearrangements that have occurred within this population of cells has not been selected for having a productive reading frame. Such cells proliferate rapidly within bursal epithelial buds of normal morphology. In addition, despite reduced levels of endogenous light chain rearrangement, those light chain rearrangements that have occurred have undergone variable region diversification by gene conversion. Therefore, although surface expression of an Ig receptor is required for bursal colonization and the induction of gene conversion, the specificity encoded by the prediversified receptor is irrelevant and, consequently, there is no obligate ligand for V(D)J-encoded determinants of prediversified avian cell surface IgM receptor.
禽类B细胞前体中的免疫球蛋白基因重排产生多样性有限的表面Ig受体。有人提出，这些受体编码的特异性通过识别法氏囊内的内源性配体在B细胞谱系发育中起关键作用。为了直接解决这个问题，我们通过体内逆转录病毒基因转移，将缺乏可变区结构域的截短表面IgM引入发育中的B前体中。表达这种截短受体的细胞缺乏内源性表面IgM，并且在这群细胞中发生的低水平内源性Ig重排没有被选择用于产生有功能的阅读框。这些细胞在形态正常的法氏囊上皮芽内迅速增殖。此外，尽管内源性轻链重排水平降低，但已经发生的那些轻链重排通过基因转换经历了可变区多样化。因此，尽管Ig受体的表面表达对于法氏囊定植和基因转换的诱导是必需的，但预多样化受体编码的特异性是无关紧要的，因此，对于预多样化禽类细胞表面IgM受体的V(D)J编码决定簇不存在必需的配体。
