Control of differentiation and function of hematopoietic cells by, BCL6 and AP-1 family

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The proto-oncogene bcl-6 and c-fos are ubiquitously expressed in various tissues, and play important role for the differentiation, proliferation, apoptosis and oncogeneisis. In this study, I focused on the function of bcl-6 and c-fos for the hematologic cells, using transgenic and gene deficient mice.1. Function of Bcl-6 on erythroid differentiationBcl-6 detected in the TER119highCD7lhigh subset of erythroblasts in the spleen of neonatal mice may be required to retain the erythroblasts in the cell proliferation stage. In addition, we found that ABCG-2 is also expressed in erythroblast of all of the maturation stage.2. Function of Bcl-6 on dendritic cell differentiationBcl-6 deficient mice showed decreased umber of dendritic cells in spleen. Especially CD8+ subfraction of dendriti cells was completely deficient,.3. Function ofBCL6 on B cell differentiationWe have found that ADAR1 (RNA-editing adenosine deaminase) is one of the target gene of BCL6, and loss of Bc16 cause the higher frequency of somatic hypermultation on B cells.4. Effect of c-Fos ro the regulation of TCRβ recombination.We have found that c-fos directly promotes RAG1/2 binding to the RSS and regulate TCRβ recombination ordering and allelic exclusion.5. Analysis of hematopoietic niche in c-Fos deficient mice.We have found that Magakaryocyte-like cells are appeared in the spleen of c-Fos deficient mice and play an important role in the hematopoietic niche.