title: Peripheral blood CD27+ IgG+ B cells rapidly proliferate and differentiate into immunoglobulin-secreting cells after exposure to low CD154 interaction.
abstract: In vitro CD40 stimulation of human B cells isolated from lymphoid organs is dominated by memory B cells undergoing faster proliferation and higher differentiation than naive B cells. In contrast, we previously reported that blood memory B cells mainly differentiate into immunoglobulin-secreting cells in response to CD40 stimulation. However, variations in CD40-CD154 interaction are now recognized to influence B-cell fate. In this study, we have compared the in vitro response of blood CD27(-) and CD27(-) IgG(-) to CD27(+) and CD27(+) IgG(+) B cells following low-density exposure to CD154 in the presence of a mixture of interleukin-2 (IL-2), IL-4 and IL-10. The evolution of these cell populations was monitored during initiation and following long-term stimulation. Over a 5-day period, CD27(+) B cells underwent differentiation into immunoglobulin-secreting cells more readily than CD27(-) cells, and CD27(+) IgG(+) B cells gave rise to a near homogeneous population of CD19(+) CD27(++) CD38(+) IgG(lo) cells capable of high immunoglobulin G (IgG) secretion. During the same period, CD27(-) IgG(-) B cells partially became CD19(++) CD27(-) CD38(-) IgG(++) cells but showed no IgG secretion. Long-term stimulation revealed that CD27(+) IgG(+) B cells retained a high expansion capacity and could maintain their momentum towards differentiation over naive B cells. In addition, long-term stimulation was driving CD27(-) IgG(-) and total CD19(+) B cells to evolve into similar CD27(+) and CD27(-) subsets, suggesting naive homeostatic proliferation. Overall, these results tend to reconcile memory B cells from blood and lymphoid organs regarding their preferential differentiation capacity compared to naive cells, and further suggest that circulating memory IgG(+) cells may be intrinsically prone to rapid activation upon appropriate stimulation.
authors.affiliation: Héma-Québec, Ingénierie cellulaire, Recherche et développement, Québec, Canada.
authors.forename: Jessie F
authors.initials: JF
authors.lastname: Fecteau
authors.forename: Annie
authors.initials: A
authors.lastname: Roy
authors.forename: Sonia
authors.initials: S
authors.lastname: Néron
mesh_terms: D000921:Antibody-Producing Cells / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology* / Q000494:pharmacology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D016753:Interleukin-10 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D016753:Interleukin-10; D023201:CD40 Ligand; D015847:Interleukin-4