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

Abstract

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.