Our immunology lab is trying to find genes expressed during B cell differentiation from the hematopoietic stem cells and to elucidate their gene expression regulatory mechanisms. The IgJ gene is expressed only after the terminal differentiation of B cells into plasma cells. The expressed IgJ chain is incorporated into the IgM pentamer or IgA dimer and is necessary for both the cellular and mucosal secretion of antibodies. Its neighboring Crlz1 gene was shown to be expressed specifically in the pre-B cell stage. The function of Crlz1, which we are working very hard to elucidate, could be related to leukemia such as B cell lymphoma, because the Crlz1 gene has been cloned by a yeast-2-hybrid technique using the CBFβ subunit of leukemia-causing CBF (Runx/CBFβ) transcription factor as a probe.

The expression of two neighboring Crlz1 and IgJ genes was shown to be regulated dynamically during B cell development at the chromatin level. The cis-acting DNA regulatory elements and trans-acting protein binding factors have been searched and characterized over the chromatin of the Crlz1-IgJ gene locus. The elucidation of transcriptional environment for the Crlz1 and IgJ genes, which we are currently working for very hard, will certainly help to understand the B cell development and the process of antibody production.

In the future, we are planning to extend our research to the field of hematopoietic stem cells to examine their self-renewal and pluripotency. We are also interested in elucidating the pathophysiology of autoimmune and allergic diseases. For the latter study, we are currently working to elucidate transcription regulatory mechanisms of the immunosuppressive IL-10 and TGF-β cytokine genes, which brake the over-reacting immune responses such as autoimmune and allergic diseases.