B-Cells induce regulatory T cells through TGF-ß/IDO production in A CTLA-4 dependent manner.

A number of studies have suggested that B cell mediated-regulation contributes to the establishment of immunological tolerance. However, the precise mechanisms by which regulatory B cells establish and maintain tolerance in humans remain to be determined. The objective of the current study is to understand the cellular and molecular bases of B-cell regulatory functions in humans. To describe the mechanisms regulating the functional plasticity of regulatory B cells, we used an in vitro co-culture model based on autologous mixed lymphocyte cultures involving freshly isolated B and T cells. The results show that activated B cells regulate T cell proliferation through producing transforming growth factor (TGF)-ß and indoleamine 2,3-dioxygenase (IDO). The production of TGF-ß and IDO leads to the induction of not only "natural" regulatory T cells but also of TGF-ß-producing CD4(+) T cells and IL-10-producing regulatory T cells. Furthermore, we evidenced for the first time that CTLA-4 induces B-cells to produce IDO and to become effective induced regulatory B cells (iBregs). This study emphasizes a novel regulatory axis and open news insights in how to manage regulatory B cell functions in autoimmunity.

[Acquired factor XI inhibitor and chronic lymphocytic leukemia]. / Allongement du TCA chez un patient atteint de leucémie lymphoïde chronique : à propos de la très rare découverte d'un autoanticorps antifacteur XI.

Autoimmune phenomena, most frequently autoimmune hemolytic anemia, is a well-known complication of lymphoproliferative diseases. We report a very rare association of a chronic lymphocytic leukemia with an acquired factor XI inhibitor. A 87-year-old man presented with auto-immune hemolytic anemia. He had untreated chronic lymphocytic leukemia for the past three years and renal insufficiency. Before surgical procedure for arteriovenous fistula, we discovered a very prolonged activated partial thromboplastin time (APTT), and an acquired factor XI inhibitor was detected. The patient was successfully treated with immunosuppressive therapy. Among patients with lymphoproliferative disorders the discovery of a prolonged APTT implies to search for rare autoimmune phenomena like acquired coagulation factor inhibitors.