B lymphocyte sensitivity to IgM receptor ligation is independent of maturation stage and locally determined by macrophage-derived IFN-beta

International Immunology
J DemengeotA Coutinho

Abstract

Compartmentation of B lymphocyte populations is associated with differences in both development stage and sensitivity to Ig (sIg)-dependent triggering. In order to characterize the factors that contribute in setting the level of sensitivity of a B cell, we quantified sIgM-dependent regulation of Ig secretion in purified mature and immature B cells after ex vivo and in vivo modification of their environment. These analyses formally demonstrate that the bone marrow (BM) microenvironment locally induces high B cell sensitivity to sIgM ligation irrespective of differentiation stage. We further provide evidence that BM macrophages create a dominant environment that enhances B cell sensitivity to B cell receptor triggering. Finally, using ex vivo assays as well as type I IFN receptor-deficient mice we show that IFN-beta produced by resident BM macrophages is necessary and sufficient to define B cell sensitivity. Implications of these findings for the understanding of B cell selection processes are discussed.

Citations

Jan 19, 2000·Immunology Today·S Marshall-ClarkeJ Hassan
Feb 27, 2003·Journal of Autoimmunity·Déborah BraunJocelyne Demengeot
Jun 1, 2006·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Miho HayashidaJunichiro Mizuguchi
Oct 28, 1998·Proceedings of the National Academy of Sciences of the United States of America·K P Lam, K Rajewsky
Sep 20, 2007·Proceedings of the National Academy of Sciences of the United States of America·Margarida Almeida SantosJocelyne Demengeot
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Apr 20, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ana Inés LalannePaulo Vieira
Jul 23, 2021·The Journal of Experimental Medicine·Cecilia B CavazzoniAndre M Vale

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