Differential responses of human B-lymphocyte subpopulations to graded levels of CD40-CD154 interaction.
Naïve and memory B-lymphocyte populations are activated by CD154 interaction through cell-surface CD40. This interaction plays an important role in the regulation of the humoral immune response, and increasing evidence indicates that fine variation in CD40 binding influences B lymphocytes, macrophages and dendritic cells in murine models. Here we have investigated whether and how variations in the intensity of the CD40-CD154 interaction could contribute to differential regulation of human B-lymphocyte populations. Proliferation and differentiation of B lymphocytes were monitored in response to graded levels of CD40 stimulation in the presence of interleukin (IL)-2, IL-4 and IL-10. Our results show that the level of CD154 binding to CD40 on B lymphocytes can directly influence the evolution of CD19(+) CD27(-) and CD19(+) CD27(+) cell populations. Furthermore, proliferation, global expansion of CD19(+) cells and emergence of CD38(++) CD138(+) cells, as well as immunoglobulin G (IgG) and IgM secretion, were affected by the level of exposure of B lymphocytes to CD154. These results suggest that the CD40-CD154 interaction is more like a rheostat than an on/off switch, and its variation of intensity may play a role in the regulation of B-lymphocyte activation following the primary and/or secondary humoral immune response.
Néron
Sonia
S
Héma-Québec, Ingénierie Cellulaire, Recherche et Développement, Sainte-foy, Canada. Sonia.Neron@hema-quebec.qc.ca
Racine
Claudia
C
Roy
Annie
A
Guérin
Matthieu
M
D016175:B-Lymphocyte Subsets / Q000276:immunology*; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000032:analysis / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D010766:Phosphorylation; D014443:Tyrosine / Q000378:metabolism
D019013:CD40 Antigens; D023201:CD40 Ligand; D014443:Tyrosine