IL-15 and IL-15 receptor selectively regulate differentiation of common mucosal immune system-independent B-1 cells for IgA responses

We show in this report a new regulatory role for IL-15 and IL-15R in the de velopment of B-l cells and their differentiation into IgA-producing cells. Mucosal IgA levels were found to be inhibited by anti-IL-15 m4b treatment i n vivo, but enhanced by administration of rIL-15, while serum IgA levels re mained unaffected. Mucosal B-l cells preferentially proliferated in respons e to IL-15 in vitro. When mucosal B-l and B-2 cells were separated into sur face (s)IgM(+)sIgA(-) and sIgM(-)sIgA(+) fractions, IL-15R-specific mRNA wa s found to be predominant in both sIgM(+)sIgA(-) and sIgM(-)sIgA(+) B-l cel ls at a much higher level than B-2 cells. Further, incubation of these diff erent subsets of B-l and B-2 cells with IL-15 resulted in greater enhanceme nt of the corresponding receptor expression by B-I subset when compared wit h B-2 fraction. Interestingly, de novo isolated sIgM(+)sIgA(-) B-l, but not sIgM(+)sIgA(-) B-2, cells were already class-switched cells because the ge rmline Ca transcript was detected and was then further enhanced by IL-15, I L-15 also supported differentiation of both sIgM(+)sIgA(-) and sIgM(-)sIgA( +) B-l cells into IgA-producing cells. Taken together, these findings sugge st that IL-15 is a critically important cytokine for the differentiation of both sIgM(+),IgA(-) and sIgM(-)sIgA(+) B-l cells expressing IL-15R into Ig A-producing cells in mucosal tissues.