Arachidonate 5-Lipoxygenase Establishes Adaptive Humoral Immunity by Controlling Primary B Cells and Their Cognate T-Cell Help

作者：Nagashima Tsutomu; Ichimiya Shingo^*; Kikuchi Tomoki; Saito Yoshiyuki; Matsumiya Hiroshi; Ara Shihoko; Koshiba Shigeru; Zhang Jun; Hatate Chizuru; Tonooka Akiko; Kubo Terufumi; Ye Rui Carrie; Hirose Bungo; Shirasaki Hideaki; Izumi Takashi; Takami Tsuyoshi; Himi Tetsuo; Sato Noriyuki

来源：American Journal Of Pathology, 2011, 178(1): 222-232.

DOI：10.1016/j.ajpath.2010.11.033

In this study, we report the unique role of arachidonate 5-lipoxygenase (Alox5) in the regulation of specific humoral immune responses. We previously reported an L22 monoclonal antibody with which human primary resting B cells in the mantle zones of lymphoid follicles are well-defined. Proteomics analyses enabled identification of an L22 antigen as Alox5, which was highly expressed by naive and memory B cells surrounding germinal centers. Cellular growth of mantle cell lymphoma cells also seemed to depend on Alox5. Alox5(-/-) mice exhibited weak antibody responses specific to foreign antigens at the initial and recall phases. This was probably attributable to the low number of follicular and memory B cells and the functional loss of interleukin-21-mediated responses of follicular B cells. Moreover, Alox5(-/-) mice could not fully foster the development of follicular B helper T (Tfh) cells even after immunization with foreign antigens. Further experiments indicated that Alox5 affected mortality in experimentally induced enterocolitis in germ-prone circumstances, indicating that Alox5 would endow immunologic milieu. Our results illustrate the novel role of Alox5 in adaptive humoral immunity by managing primary B cells and Tfh cells in vivo. (Am J Pathol 2011, 178: 222-232; DOI: 10.1016/j.ajpath.2010.11.033)

• 出版日期2011-1