Tight regulation of IFN-gamma transcription and secretion in immature and mature B cells by the inhibitory MHC class I receptor, Ly49G2.
To complete their maturation and to 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 sites of inflammation, enabling their targeting to the spleen to allow their final maturation. This inhibition is mediated by IFN-gamma, which is transcribed and secreted at low levels by these immature B cells and is down-regulated at the mature stage. The activating MHC class I receptor, Ly49D, which is expressed at high levels on immature B cells, stimulates this IFN-gamma secretion. In this study we show that B cells coexpress the inhibitory MHC class I receptor, Ly49G2. In addition, we demonstrate a tight regulation in the expression of the Ly49 family members on B cells that depends on their cell surface levels. High levels of Ly49G2 have a dominant inhibitory effect on Ly49D expressed at low levels on immature bone marrow and mature B cells, resulting in inhibition of IFN-gamma secretion. However, low levels of the inhibitory receptor, Ly49G2, coexpressed with high levels of the activating receptor, Ly49D, on the immigrating immature B cells enable the secretion of specific low levels of IFN-gamma. This expression pattern insures the inhibitory control of peripheral immature B cell to prevent premature encounter with an Ag while enabling entry to the lymph nodes during the mature stage.
Hart
Gili
G
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Flaishon
Liat
L
Becker-Herman
Shirly
S
Shachar
Idit
I
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology
D015395:Histocompatibility Antigens Class I; C452844:Ly49G2 receptor; D011971:Receptors, Immunologic; D007371:Interferon-gamma