Homeostatic ‘bystander’ proliferation of human peripheral blood B cells in response to polyclonal T-cell stimulationin vitro

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.

Memory B Cell Activation, Broad Anti-influenza Antibodies, and Bystander Activation Revealed by Single-Cell Transcriptomics

“…Nevertheless, our integrated strategy of single-cell sequencing and Rep-seq offers a direct route to characterization of these non-vaccine-specific yet vaccine-elicited antibodies. Our results also suggest that bystander activation is confined to a small number of clones by an unknown mechanism, perhaps related to the localization of activated T cells (Jasiulewicz et al, 2015;Juy et al, 1987;Lanzavecchia et al, 1983).…”

The influence of a single hemodialysis procedure on human T lymphocytes

“…In the anti-CD3 stimulated PBMC samples from 7 HD patients before and after single hemodialysis procedure dynamic parameters of proliferation kinetics of CD4 + and CD8 + T cells were measured with DCT method and analyzed using our own protocol published and validated earlier 11,14 . Proliferating lymphocytes were selected on the basis of forward and side scatter characteristics (Fig.…”

“…Since the function of B lymphocytes largely depends on the activation of CD4 + cells, their impaired activity can encourage the progression of immune deficiency manifested as a reduced response of HD patients to vaccination against hepatitis B 2 , tetanus 12 or pneumococcus 13 . Indeed, our latest results show that T cell-dependent activity of B cells is significantly impaired in HD patients 14 . Reasons of these abnormalities are still unclear.…”

Transcriptional program of memory B cell activation, broadly binding anti-influenza antibodies, and bystander activation after vaccination revealed by single-cell transcriptomics

“…Nevertheless, our integrated strategy of single-cell and Rep-seq offers a direct route to characterization of these non-vaccine-specific yet vaccine-elicited antibodies. Our results also indicate that bystander activation is confined to a small number of clones by an unknown mechanism, perhaps related to the presence of activated T cells (38–40).…”