Quantal and graded stimulation of B lymphocytes as alternative strategies for regulating adaptive immune responses

Nat Commun. 2013;4:2406. doi: 10.1038/ncomms3406.


Lymphocytes undergo a typical response pattern following stimulation in vivo: they proliferate, differentiate to effector cells, cease dividing and predominantly die, leaving a small proportion of long-lived memory and effector cells. This pattern results from cell-intrinsic processes following activation and the influence of external regulation. Here we apply quantitative methods to study B-cell responses in vitro. Our results reveal that B cells stimulated through two Toll-like receptors (TLRs) require minimal external direction to undergo the basic pattern typical of immunity. Altering the stimulus strength regulates the outcome in a quantal manner by varying the number of cells that participate in the response. In contrast, the T-cell-dependent CD40 activation signal induces a response where division times and differentiation rates vary in relation to stimulus strength. These studies offer insight into how the adaptive antibody response may have evolved from simple autonomous response patterns to the highly regulable state that is now observed in mammals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / drug effects
  • Adaptive Immunity / immunology*
  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology*
  • CD40 Antigens / metabolism
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Cell Proliferation / drug effects
  • Female
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Models, Immunological
  • Oligodeoxyribonucleotides / pharmacology
  • Toll-Like Receptor 9 / metabolism


  • CD40 Antigens
  • CPG-oligonucleotide
  • Lipopolysaccharides
  • Oligodeoxyribonucleotides
  • Toll-Like Receptor 9