IL-15 regulates immature B-cell homing in an Ly49D-, IL-12 , and IL-18 dependent manner.
To complete their maturation and participate in the humoral immune response, immature B cells that leave the bone marrow are targeted to specific areas in the spleen, where they differentiate into mature cells. Previously, we showed that immature B cells actively down-regulate their integrin-mediated migration to lymph nodes or to sites of inflammation, enabling their targeting to the spleen for final maturation. This inhibition is mediated by IFN-gamma, which is transcribed and secreted at low levels by these immature B cells; IFN-gamma expression is extinguished following B-cell maturation. Stimulation of the MHC class I receptor, Ly49D, triggers a signaling cascade that increases transcription of both IL-12 (p40) and IL-18; these, in turn, induce the secretion of IFN-gamma. In the present study, we demonstrate that Ly49D-dependent secretion of IL-12 and IL-18 induces IL-15 expression by immature B cells, and that these 3 factors together regulate IFN-gamma production that inhibits their ability to home to the lymph nodes or to sites of inflammation. Thus, IL-15 controls immature B-cell homing, resulting in shaping the B-cell repertoire to enable an efficient immune response.
Hart
Gili
G
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Avin-Wittenberg
Tamar
T
Shachar
Idit
I
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology* / Q000378:metabolism; D019898:Autocrine Communication / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000276:immunology* / Q000378:metabolism; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020382:Interleukin-18 / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D055650:NK Cell Lectin-Like Receptor Subfamily A; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D055630:Receptors, NK Cell Lectin-Like; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology; D014158:Transcription, Genetic / Q000276:immunology
D000950:Antigens, Ly; D053762:Interleukin-12 Subunit p40; D019409:Interleukin-15; D020382:Interleukin-18; C527092:Klra4 protein, mouse; D037181:Lectins, C-Type; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055630:Receptors, NK Cell Lectin-Like; D007371:Interferon-gamma