Pax5 is indispensable for the commitment of early lymphoid progenitors to the B cell lineage as well as for the development of B cells. To better understand the functional importance of Pax5 at the later stages of B cell differentiation, we established a Pax5-deficient DT40 B cell line. The Pax5(-/-) cells exhibited slower growth, decreased surface IgM expression, and total loss of B cell receptor signaling. Moreover, the expression of the plasma cell-characteristic transcription factors Blimp-1 and XBP-1 were significantly upregulated and the expression of Bcl-6 diminished in the Pax5(-/-) cells, and this alteration was normalized by restored Pax5 expression. The Pax5-deficient cells further manifested substantially elevated secretion of IgM into the supernatant, another characteristic of plasma cells. These results indicate that downregulation of Pax5 function promotes the plasma cell differentiation of B cells.

Summary CD4+ CD25+ + + + regulatory T (T reg ) cells play a critical role in the maintenance of peripheral tolerance and the prevention of autoimmunity. In the present study, we have explored the characteristics of CD4

The Ikaros family transcription factor Aiolos is important for B cell function, since B cells of Aiolos‐null mutant mice exhibit an activated phenotype, enhanced B‐cell receptor (BCR) signalling response and develop a systemic lupus erythematosus (SLE) type autoimmune disease. Aiolos has also been reported to interact with anti‐apoptotic Bcl‐2 and Bcl‐xL in T cells, but whether Aiolos regulates cell death has not been studied in B cells. Here we show that the disruption of Aiolos in the DT40 B cell line induces a cell death sensitive phenotype, as the Aiolos−/− cells are more prone to apoptosis by nutritional stress, BCR cross‐linking, UV‐ or γ‐irradiation. Furthermore, the Aiolos−/− cells have defective Ig gene conversion providing evidence that Aiolos is needed for the somatic diversification of the BCR repertoire. The re‐expression of DNA‐binding isoform Aio‐1 was able to restore the gene conversion defect of the Aiolos‐deficient cells, whereas the introduction of dominant negative isofom Aio‐2 had no effect on gene conversion, thus demonstrating the functional importance of alternative splicing within Ikaros family. Although the Aiolos−/− cells exhibit reduced expression of activation‐induced cytidine deaminase (AID), ectopic AID overexpression did not restore the gene conversion defect in the Aiolos−/− cells. Our findings indicate that Aiolos may regulate gene conversion in an AID independent manner.

The bursa of Fabricius plays a central role in the development of the antibody‐producing B‐lymphocyte lineage in birds. It consists of more than 10 000 follicles surrounded by connective tissue. These follicles provide an appropriate microenvironment for generating a primary repertoire of antibodies. Immunoglobulin gene diversification is achieved by gene conversion and is antigen independent. Follicular B cells undergo very rapid cell division while expressing several genes also expressed in proliferating germinal centre B cells, such as AID , UNG , Pax5 and Bcl6 . Bursal B cell line DT40 provides a unique model system for gene‐targeting studies clarifying the B‐cell development, function and Ig diversification. Key Concepts: Bursa of Fabricius is the primary site for B‐cell development and antibody repertoire formation in birds. Antibody diversification in the bursa of Fabricius is antigen independent and occurs mostly by Ig gene conversion. Bursal derived DT40 B cell line provides a reverse genetic model to study molecular function of B cells.