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Pax5: the guardian of B cell identity and function

Abstract

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 VH-DJH 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.

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Figure 1: Functional domains and interacting proteins of Pax5.
Figure 2: B cell lineage commitment by Pax5.
Figure 3: Pax5-dependent gene expression.
Figure 4: Pax5-dependent contraction of the Igh locus in pro-B cells.
Figure 5: Chromosomal translocations involving PAX5 in human B cell malignancies.

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Acknowledgements

We thank S. Nutt and T. Jenuwein for comments on the manuscript. Supported by Boehringer Ingelheim (M.B.), the Austrian Industrial Research Promotion Fund (M.B.), a Spanish 'Ramon y Cajal' investigator grant (C.C.) and Fondo de Investigaciónes Sanitarias (PI04/0261; C.C.).

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Cobaleda, C., Schebesta, A., Delogu, A. et al. Pax5: the guardian of B cell identity and function. Nat Immunol 8, 463–470 (2007). https://doi.org/10.1038/ni1454

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