期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 178, 期 1, 页码 222-232出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2010.11.033
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资金
- Japan Society of Promotion of Science [20590347]
- Japan Rheumatism Foundation
- Akiyama Foundation
- Suhara Memorial Foundation
- Grants-in-Aid for Scientific Research [23590405, 22659075] Funding Source: KAKEN
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)
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