IMMUNOGLOBULIN GENE REARRANGEMENT IN B-CELL DEFICIENT MICE GENERATED BY TARGETED DELETION OF THE J(H) LOCUS
IMMUNOGLOBULIN GENE REARRANGEMENT IN B-CELL DEFICIENT MICE GENERATED BY TARGETED DELETION OF THE J(H) LOCUS
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DOI：
10.1093/intimm/5.6.647
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发表时间：
1993-06-01
影响因子：
4.4
通讯作者：
HUSZAR, D
中科院分区：
文献类型：
--
作者：
CHEN, JZ;TROUNSTINE, M;HUSZAR, D
B淋巴细胞分化的特征是一系列有序的Ig基因组装和表达事件。在大多数正常B细胞中，Ig重链(H)链基因的组装和表达先于轻链基因(L)。为了确定免疫球蛋白重链蛋白在B细胞发育和L链基因重排中的作用，我们产生了由于胚胎干细胞中J(H)基因片段的定向缺失而无法组装免疫球蛋白H链基因的小鼠。这种缺失的纯合子小鼠在骨髓和外周缺乏slg+B细胞。这些小鼠的B细胞分化受阻于大的CD43+前体阶段。然而，这些前体B细胞确实在缺乏u H链蛋白的情况下低水平地组装kappa L链基因。这些数据表明，kappa L链基因在体内的重排并不一定需要mH链基因的重排和表达。MU链的表达可能通过促进大的CD43+细胞向小的CD43-Pre-B细胞的分化而促进有效的L链基因重排或重排轻链基因的细胞的生存。
B lymphocyte differentiation is characterized by an ordered series of Ig gene assembly and expression events. In the majority of normal B cells, assembly and expression of Ig heavy (H) chain genes precedes that of light (L) chain genes. To determine the role of the Ig heavy chain protein in B cell development and L chain gene rearrangement, we have generated mice that cannot assemble Ig H chain genes as a result of targeted deletion of the J(H) gene segments in embryonic stem cells. Mice homozygous for this deletion are devoid of slg+ B cells in the bone marrow and periphery. B cell differentiation in these mice is blocked at the large, CD43+ precursor stage. However, these precursor B cells do assemble kappa L chain genes at a low level in the absence of mu H chain proteins. These data demonstrate that rearrangement and expression of the mu H chain gene is not absolutely required for kappa L chain gene rearrangement in vivo. Expression of mu chains may facilitate either efficient L chain gene rearrangement or the survival of cells that have rearranged light chain genes by promoting the differentiation of large, CD43+ to small, CD43- pre-B cells.