Tretter Theresa, Ross Ashley E, Dordai Dominic I, Desiderio Stephen
Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
J Exp Med. 2003 Dec 15;198(12):1863-73. doi: 10.1084/jem.20030729. Epub 2003 Dec 8.
During B lymphoid ontogeny, assembly of the pre-B cell receptor (BCR) is a principal developmental checkpoint at which several Src-related kinases may play redundant roles. Here the Src-related kinase Blk is shown to effect functions associated with the pre-BCR. B lymphoid expression of an active Blk mutant caused proliferation of B progenitor cells and enhanced responsiveness of these cells to interleukin 7. In mice lacking a functional pre-BCR, active Blk supported maturation beyond the pro-B cell stage, suppressed VH to DJH rearrangement, relieved selection for productive heavy chain rearrangement, and stimulated kappa rearrangement. These alterations were accompanied by tyrosine phosphorylation of immunoglobulin beta and Syk, as well as changes in gene expression consistent with developmental maturation. Thus, sustained activation of Blk induces responses normally associated with the pre-BCR.
在B淋巴细胞发育过程中，前B细胞受体（BCR）的组装是一个主要的发育检查点，几种与Src相关的激酶可能在该检查点发挥冗余作用。本文表明，与Src相关的激酶Blk可影响与前BCR相关的功能。活性Blk突变体的B淋巴细胞表达导致B祖细胞增殖，并增强这些细胞对白介素7的反应性。在缺乏功能性前BCR的小鼠中，活性Blk支持B细胞前体阶段之后的成熟，抑制VH到DJH重排，解除对有生产性重链重排的选择，并刺激κ重排。这些改变伴随着免疫球蛋白β和Syk的酪氨酸磷酸化，以及与发育成熟一致的基因表达变化。因此，Blk的持续激活诱导了通常与前BCR相关的反应。
