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The Journal of Immunology, 2000, 165: 4329-4337.
Copyright © 2000 by The American Association of Immunologists

IL-15 and IL-15 Receptor Selectively Regulate Differentiation of Common Mucosal Immune System-Independent B-1 Cells for IgA Responses1

Takachika Hiroi, Manabu Yanagita, Noriyuki Ohta, Gaku Sakaue and Hiroshi Kiyono2

Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan

We show in this report a new regulatory role for IL-15 and IL-15R in the development of B-1 cells and their differentiation into IgA-producing cells. Mucosal IgA levels were found to be inhibited by anti-IL-15 mAb treatment in vivo, but enhanced by administration of rIL-15, while serum IgA levels remained unaffected. Mucosal B-1 cells preferentially proliferated in response to IL-15 in vitro. When mucosal B-1 and B-2 cells were separated into surface (s)IgM+sIgA- and sIgM-sIgA+ fractions, IL-15R-specific mRNA was found to be predominant in both sIgM+sIgA- and sIgM-sIgA+ B-1 cells at a much higher level than B-2 cells. Further, incubation of these different subsets of B-1 and B-2 cells with IL-15 resulted in greater enhancement of the corresponding receptor expression by B-1 subset when compared with B-2 fraction. Interestingly, de novo isolated sIgM+sIgA- B-1, but not sIgM+sIgA- B-2, cells were already class-switched cells because the germline C{alpha} transcript was detected and was then further enhanced by IL-15. IL-15 also supported differentiation of both sIgM+sIgA- and sIgM-sIgA+ B-1 cells into IgA-producing cells. Taken together, these findings suggest that IL-15 is a critically important cytokine for the differentiation of both sIgM+,IgA- and sIgM-sIgA+ B-1 cells expressing IL-15R into IgA-producing cells in mucosal tissues.




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