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

• Published in: International immunology Vol. 9; no. 11; pp. 1677 - 1685
• Main Authors: Demengeot, J, Vasconcellos, R, Modigliani, Y, Grandien, A, Coutinho, A
• Format: Journal Article
• Language: English
• Published: England 01.11.1997
• Subjects: Animals; B-Lymphocytes - cytology; B-Lymphocytes - immunology; B-Lymphocytes - physiology; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; Cell Differentiation - physiology; Immunoglobulin M - physiology; Interferon-beta - biosynthesis; Interferon-beta - physiology; Macrophages - metabolism; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Receptors, Fc - physiology; Sensitivity and Specificity
• ISSN: 0953-8178; 1460-2377; 1460-2377
• DOI: 10.1093/intimm/9.11.1677

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.