Mechanism s regulating the gene rearrangements in immune system

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The most unque character in acquired immunity is that genes encoding receptors for antigen undergo rearrangements by DNA recombination to acquire and expand their function in the immune-competent lymphocytes. Furthermore these rearrangements determine the differentiation stage of the lymphocyte. The antigen receptor genes are completed by the rearrangements of variable regions, and this enables the receptors to bind specifically to the antigen. by this, each individual lymphocyte can recognize a specific antigen and thus immune system as whole can recognize a wide variety of antigens. In addition, antibodies act as effecter to eliminate or neutralize antigens. To expand such effecter function of antibody according to the route through which the antigens invade, the constant region genes of its heavy chain also rearrange during activation of B lymphocyte (class switch recombination, CSR).In this study, we tried to elucidate the molecular mechanisms controlling the rearrangements per se and target gene specificity by analyzing transcription factors involved in the rearrangement process. We found that the transcription factors, Pax5, E2A, SIP, NF_KB, IRF4, and Runx1-3 are involved and important in the specific regulation of target gene selection and expression of AID gene that is essential for CSR. These factors together with Id2 form epigenetic regulatory circuits downstream to TFG-β signal. We also found that expression of these factors is affected by the micro-environment formed by a dynamic reorganization and neogenesis of the secondary and tertiary lymphoid tissues, and in some case these factors showed a redundant function but in other case they Showed opposite function. Such mechanism increases the complexity of the regulation.In addition, using a combination of stimuli we established an efficient method to induce CSR specifically to IgA in vitro that has been very difficult up to now.