Contribution of secondary Igkappa rearrangement to primary immunoglobulin repertoire diversification
Contribution of secondary Igkappa rearrangement to primary immunoglobulin repertoire diversification
复制标题
二次 Igkappa 重排对初级免疫球蛋白库多样化的贡献
DOI：
10.1016/j.molimm.2016.09.006
复制
发表时间：
2016-10-01
影响因子：
3.6
通讯作者：
Liu，Feifei
中科院分区：
文献类型：
--
作者：
Li，Shufang;Liu，Wei;Liu，Feifei
与DNA和DNA/组蛋白复合物反应的抗体是自身免疫B6. MRL/MpJ-Faslpr小鼠中主要免疫球蛋白库的显著特征。这些小鼠是缺陷的Fas受体，这是至关重要的自身反应性B细胞通过外源性途径凋亡。在本研究中，我们探讨了骨髓小前B和不成熟B细胞的成年B6. MRL-Faslpr小鼠和MRL/MpJ-Faslpr小鼠，分别含有自身反应性B细胞抗原受体（BCR）和表现出自身免疫综合征，表现出增强的受体编辑模式的可能性。事实上，显示FASlprpre B和未成熟B细胞具有比生产性（P）原发性VκJκ重排更多的非生产性（β）进行中的置换。值得注意的是，这些被取代的初级重排的P与P比值为1：2，因此表明κ轻链的产生似乎不会抑制二级重排。此外，我们还发现了多种非典型重排，如Vκ cRS（隐蔽重组信号）裂解。这些结果表明，在狼疮易感小鼠和对照小鼠的骨髓B细胞的某些发育窗口期间，轻链二级重排的发生类似地作为非选择性模式持续存在，并且独立于BCR自身反应性，并使我们提出二级、从头Ig κ重排增加BCR多样性的功能。
Abs reactive to DNA and DNA/histone complexes are a distinguished characteristic of primary immunoglobulin repertoires in autoimmune B6.MRL-Faslprand MRL/MpJ-Faslprmice. These mice are defective in Fas receptor, which is critical for the apoptosis of autoreactive B cells by an extrinsic pathway. In the present study, we explored the possibility that bone marrow small pre-B and immature B cells from adult B6.MRL-Faslprmice and MRL/MpJ-Faslprmice respectively, which contain autoreactive B-cell antigen receptors (BCR) and manifest autoimmune syndromes, exhibit enhanced receptor editing patterns. Indeed, FASlprpre B and immature B cells were shown to possess more ongoing replacements of non-productive (nP) than productive (P) primary VκJκ rearrangements. Significantly, the P vs nP ratios of these replaced primary rearrangements were 1:2, thus indicating that κ light-chain production appears not to inhibit secondary rearrangements. In addition, we identified multiple atypical rearrangements, such as Vκ cRS (cryptic recombination signals) cleavages. These results suggest that the onset of light chain secondary rearrangements persists similarly as a non-selected mode and independent of BCR autoreactivity during certain developmental windows of bone marrow B cells in lupus-prone mice and control, and leads us to propose the function of secondary,de novoIgκ rearrangements to increase BCR diversity.