Kövesdi Dorottya, Bell Sarah E, Turner Martin
Laboratory of Lymphocyte Signalling and Development; The Babraham Institute; Babraham, Cambridge UK.
Self Nonself. 2010 Apr;1(2):144-153. doi: 10.4161/self.1.2.11796. Epub 2010 Mar 11.
Mice lacking either CD19 or p110δ have reduced numbers of marginal zone and B1 B cells but normal numbers of naïve B2 cells which occupy the follicles of the lymphoid organs. We show here that mice lacking both CD19 and p110δ have normal B cell development in the bone marrow but have a significant reduction in the number of naïve B2 cells in the bone marrow, spleen and lymph nodes. These p110δ/CD19 double mutant B cells show a survival defect and reduced responsiveness to the pro-survival cytokine BAFF despite normal NFκB2/p100 processing and elevated expression of Bcl-2. Although the combined loss of p110δ and CD19 did not increase switching to Ig-lambda in immature B cells, mature B lymphocytes from the lymph nodes of p110δ/CD19 double mutant mice express highly elevated levels of mRNA encoding RAG-1 and RAG-2, which confirms the existing synergy between CD19 and p110δ-mediated signaling.
缺乏CD19或p110δ的小鼠边缘区和B1 B细胞数量减少，但占据淋巴器官滤泡的初始B2细胞数量正常。我们在此表明，同时缺乏CD19和p110δ的小鼠骨髓中B细胞发育正常，但骨髓、脾脏和淋巴结中的初始B2细胞数量显著减少。这些p110δ/CD19双突变B细胞表现出存活缺陷，尽管NFκB2/p100加工正常且Bcl-2表达升高，但对促存活细胞因子BAFF的反应性降低。虽然p110δ和CD19的联合缺失并未增加未成熟B细胞向Ig-λ的类别转换，但来自p110δ/CD19双突变小鼠淋巴结的成熟B淋巴细胞表达编码RAG-1和RAG-2的mRNA水平显著升高，这证实了CD19和p110δ介导的信号传导之间存在协同作用。
