Peripheral blood CD27+ IgG+ B cells rapidly proliferate and differentiate into immunoglobulin-secreting cells after exposure to low CD154 interaction

Authors

  • Jessie F. Fecteau,

    1. Héma-Québec, Ingénierie cellulaire, Recherche et développement, Québec, Canada
    2. Département de biochimie et microbiologie, Faculté des sciences et de génie, Université Laval, Québec, Canada
    Search for more papers by this author
  • Annie Roy,

    1. Héma-Québec, Ingénierie cellulaire, Recherche et développement, Québec, Canada
    Search for more papers by this author
  • Sonia Néron

    1. Héma-Québec, Ingénierie cellulaire, Recherche et développement, Québec, Canada
    2. Département de biochimie et microbiologie, Faculté des sciences et de génie, Université Laval, Québec, Canada
    Search for more papers by this author

S. Néron, Héma-Québec, Recherche et développement, 1070 avenue des Sciences de la vie, Québec, Québec G1V 5C3, Canada. Email: sonia.neron@hema-quebec.qc.ca
Senior author: Sonia Néron

Summary

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+ IgGlo 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.

Ancillary