Homeostatic 'bystander' proliferation of human peripheral blood B cells in response to polyclonal T-cell stimulation in vitro

Int Immunol. 2015 Nov;27(11):579-88. doi: 10.1093/intimm/dxv032. Epub 2015 May 20.

Abstract

The mechanisms of maintenance of adequate numbers of B lymphocytes and of protective levels of immunoglobulins in the absence of antigenic (re)stimulation remain not fully understood. Meanwhile, our results presented here show that both peripheral blood naive and memory B cells can be activated strongly and non-specifically (in a mitogen-like fashion) in 5-day in vitro cultures of anti-CD3- or concanavalin A (Con A)-stimulated peripheral blood mononuclear cells of healthy people. This polyclonal, bystander activation of the B cells includes multiple divisions of most of them (assessed here by the flow cytometric technique of dividing cell tracking) and significant antibody [immunoglobulin M (IgM) and IgG] secretion. Observed proliferation of the CD19(+) B cells depends on contact with stimulated T helper (Th) cells (via CD40-CD40L interaction) and on the response of B cells to secreted interleukins IL-5, IL-10 and IL-4, and is correlated with the levels of these Th-derived molecules, while it does not involve the ligation of the BCR/CD19 complex. We suggest that the effect might reflect the situation occurring in vivo as the homeostatic proliferation of otherwise non-stimulated, peripheral B lymphocytes, providing an always ready pool for efficient antibody production to any new (or cognate) antigen challenge.

Keywords: B cells; B/T cell cooperation; T cells; healthy; homeostatic proliferation; human PBMC; in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibody Formation / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Communication / immunology*
  • Cell Cycle
  • Cells, Cultured
  • Cytokines / metabolism
  • Female
  • Humans
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin M / biosynthesis
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation / immunology*
  • Lymphocyte Depletion
  • Male
  • Middle Aged
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism

Substances

  • Cytokines
  • Immunoglobulin G
  • Immunoglobulin M