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 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 Calpha 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.
Hiroi
T
T
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Yanagita
M
M
Ohta
N
N
Sakaue
G
G
Kiyono
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007274:Injections, Intraperitoneal; D019409:Interleukin-15 / Q000276:immunology / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity / Q000166:cytology; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology
D000911:Antibodies, Monoclonal; C508025:Il15ra protein, mouse; D007071:Immunoglobulin A, Secretory; D019409:Interleukin-15; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D007073:Immunoglobulin E