B lymphocyte sensitivity to IgM receptor ligation is independent of maturation stage and locally determined by macrophage-derived IFN-beta.
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.
Demengeot
J
J
Unité d'immunobiologie, CNRS URA 1961, Institut Pasteur, Paris, France.
Vasconcellos
R
R
Modigliani
Y
Y
Grandien
A
A
Coutinho
A
A
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D007075:Immunoglobulin M / Q000502:physiology; D016899:Interferon-beta / Q000096:biosynthesis / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011961:Receptors, Fc / Q000502:physiology*; D012680:Sensitivity and Specificity
D007075:Immunoglobulin M; D011961:Receptors, Fc; C035311:immunoglobulin M receptor; D016899:Interferon-beta