Cobaleda César, Schebesta Alexandra, Delogu Alessio, Busslinger Meinrad
Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Nat Immunol. 2007 May;8(5):463-70. doi: 10.1038/ni1454.
The transcription factor Pax5 is essential for commitment of lymphoid progenitors to the B lymphocyte lineage. Pax5 fulfils a dual role by repressing B lineage 'inappropriate' genes and simultaneously activating B lineage-specific genes. This transcriptional reprogramming restricts the broad signaling capacity of uncommitted progenitors to the B cell pathway, regulates cell adhesion and migration, induces V(H)-DJ(H) recombination, facilitates (pre-)B cell receptor signaling and promotes development to the mature B cell stage. Conditional Pax5 inactivation in early and late B lymphocytes revealed an essential role for Pax5 in controlling the identity and function of B cells throughout B lymphopoiesis. PAX5 has also been implicated in human B cell malignancies, as it is deregulated by chromosomal translocations in a subset of acute lymphoblastic leukemias and non-Hodgkin lymphomas.
转录因子Pax5对于淋巴祖细胞向B淋巴细胞谱系的定向分化至关重要。Pax5通过抑制B谱系“不适当”基因并同时激活B谱系特异性基因发挥双重作用。这种转录重编程将未定向祖细胞广泛的信号传导能力限制在B细胞途径，调节细胞黏附和迁移，诱导V(H)-DJ(H)重组，促进（前）B细胞受体信号传导并促进向成熟B细胞阶段的发育。在早期和晚期B淋巴细胞中条件性失活Pax5揭示了Pax5在整个B淋巴细胞生成过程中控制B细胞特性和功能方面的重要作用。PAX5也与人类B细胞恶性肿瘤有关，因为在一部分急性淋巴细胞白血病和非霍奇金淋巴瘤中它因染色体易位而失调。
