Molecular mechanisms of oral immunity : Role of IL-5 in potentiation of IgA production in mucosal lymphoid cell

Interleukin-5 (IL-5) is Produced mainly by activated T lymphocytes and mast cells.它是原始的其活性as a B cell growth factor and an IgA-enhancing factor. The IL-5 receptorIL-5R consists of two distinct membrane proteins，α和β chains. The binding of IL-5 occurs through The IL-5Rα，and the β chain forms a high affinity with IL-5Rα for the intracellular signal transduction pathway。IL-5, which has been shown to be an important cytokine for the mucosal immune systempossesses several immunological features which distinguish it from the systemic immune compartment.for example,IgA inductive tissues such as gut-associated lymphoreticular tissue (GALT) or Peyer's patches （PP）containing a high frequency of IgA-committed B cells (surface IgA D1+ sIgA D1) B cellsand Th1/Th2 cells are interconnected with IgA effector sites including intestinal lamina propriavia the common mucosal immune system . IL-5 is a major cytokine which induce…sIgA - D1+ D1 B cells to differentiate into IgA-producing plasma cells using mainly一种体外系统使用PP和mitogen-stimulated splenic B cells. Further IL-2和IL-6 have beendemonstrated to be be capable of增强IgA synthesis in vitro. An intriguing observation is that upto 40% of IgA-producing cells in the murine intestinal lamina propria arise from a pool of B-1peritoneal and lamina propria B-1 cells in mice have peritoneal cavity. peritoneal and lamina propriabeen shown to develop from a common pool and may represent a lineage from that ofconventional PP B cells. These results suggest that B - 1 cells could be important source forIgA-producing cells in mucosal tissues.我们focused our study on exploring the role of IL-5R and B-1cells in the development of IgA-producing cells in mucosa-associated tissues using the lattergene-disrupted murine model together with the background wild type mic . deletion of IL-5Rαselectively influenced the mucosal IgA responses in体内。While level of IgA in mucosal secretionswere more rduced in IL-5Rα D1-/- D1 mice than in wild type mice，IgA-producing cells的频率降低，IgA-producing cells的水平不改变。mucosal effector sites (e.g. intestinal lamina propria and nasal passage) but not in inductive sitessuch as PP and nasal-associated lymphoreticular，tissues (NALT) in IL-5Rα - 1-/- mice IgA-committed (surface IgA- D1+ tissues D1；B-1 cells mainly resided in mucosal effector tissues，while conventional sIgA B (B-2) cells formed in mucosal inductive sites of wild type mice.In contrast, In the effector tissue of IL-5Rα - D1-/- mice, sIgA - D1+ B-1 cells，B-2 cells in the inductive site，were significantly reduced. IL-5Rα was more expressed on sIgA il -1 + il -1 B-1 cells than was IL-6R，while both IL-5Rα和IL-6R were expressed on sIgA B-2 cells in wild type mice.B-1 cells produced high levels of IgA with recombinant IL-5 (IL-5) rather than of IL-6in vitro. Taken together，the findings demonstrate the IL-5/IL-5R signaling pathway is critically important for thecommon mucosal immune system (CMIS) independent sIgA - B-1 cell development and for IgAresponses in mucosal effector tissues in vivo. Less

Interleukin-5 (IL-5) is Produced mainly by activated T lymphocytes and mast cells. It was originally recognized by its activity as a B cell growth factor and an IgA-enhancing factor. The IL-5 receptor (IL-5R) consists of two distinct membrane proteins, α and β chains. The binding of IL-5 occurs through the IL-5Rα, and the β chain forms a high affinity with IL-5Rα for the intracellular signal transduction pathway. IL-5, which has been shown to be an important cytokine for the mucosal immune system, possesses several immunological features which distinguish it from the systemic immune compartment. For example, IgA inductive tissues such as gut-associated lymphoreticular tissue (GALT) or Peyer's patches (PP) containing a high frequency of IgA-committed B cells [surface IgAィイD1+ィエD1 (sIgAィイD1+ィエD1) B cells and Th1/Th2 cells are interconnected with IgA effector sites including intestinal lamina propria (i-LP) via the common mucosal immune system (CMIS). IL-5 is a major cytokine which induce … More s sIgAィイD1+ィエD1 B cells to differentiate into IgA-producing plasma cells using mainly an in vitro system using PP and mitogen-stimulated splenic B cells. Further IL-2 and IL-6 have been demonstrated to be capable of enhancing IgA synthesis in vitro. An intriguing observation is that up to 40% of IgA-producing cells in the murine intestinal lamina propria arise from a pool of B-1 precursors derived from the peritoneal cavity. Peritoneal and lamina propria B-1 cells in mice have been shown to develop from a common pool and may represent a lineage separate from that of conventional PP B cells. These results suggest that B - 1 cells could be an important source for IgA-producing cells in mucosal tissues. We focused our study on exploring the role of IL-5R and B-1 cells in the development of IgA-producing cells in mucosa-associated tissues using the latter gene-disrupted murine model together with the background wild type mice.Deletion of IL-5Rα selectively influenced the mucosal IgA responses in vivo. While levels of IgA in mucosal secretions were more rduced in IL-5RαィイD1-/-ィエD1 mice than in wild type mice, the levels of IgA in serum were not changed. The frequency of IgA-producing cells was reduced in mucosal effector sites (e.g. intestinal lamina propria and nasal passage) but not in inductive sites such as PP and nasal-associated lymphoreticular, tissues (NALT) in IL-5RαィイD1-/-ィエD1 mice IgA-committed (surface IgAィイD1+ィエD1 ; sIgAィイD1+ィエD1) B-1 cells mainly resided in mucosal effector tissues, while conventional sIgAィイD1+ィエD1 B (B-2) cells formed in mucosal inductive sites of wild type mice. In contrast, in the effector tissue of IL-5RαィイD1-/-ィエD1 mice, sIgAィイD1+ィエD1 B-1 cells, but not sIgAィイD1+ィエD1 B-2 cells in the inductive site, were significantly reduced. IL-5Rα was more expressed on sIgAィイD1+ィエD1 B-1 cells than was IL-6R, while both IL-5Rα and IL-6R were expressed on sIgAィイD1+ィエD1 B-2 cells in wild type mice. sIgAィイD1+ィエD1 B-1 cells produced high levels of IgA with recombinant IL-5 (IL-5) rather than of IL-6 in vitro. Taken together, the findings demonstrate that the IL-5/IL-5R signaling pathway is critically important for the common mucosal immune system (CMIS) independent sIgAィイD1+ィエD1 B-1 cell development and for IgA responses in mucosal effector tissues in vivo. Less