Antigen activation of human B lymphocytes bearing artificial antigen receptors

Abstract

When highly purified human and murine B cells are challenged in vitro with certain so called "T cell-independent" activators such as the polyclonal B cell activator lipopolysaccharide (LPS) or the clonally specific B cell activator dinitrophenyl-conjugated polymerized flagellin (DNP-POL), mouse, but not human, cells differentiate into immunoglobulin-secreting cells. However, results from this study show that DNP-POL can cause human B cell differentiation in a T cell-independent manner when the antigen is concentrated onto the cells via artificially incorporated palmitate-modified anti-DNP mouse IgA molecules. This response is comparable in magnitude to that induced by a T cell-dependent polyclonal B cell activator, pokeweed mitogen, in unfractionated mononuclear cell cultures, suggesting that DNP-POL induced polyclonal B cell differentiation. DNP-POL binding to the artificial receptor molecules on B cells did not cause cellular proliferation, even in unfractionated mononuclear cell populations. These results are similar to those obtained in previous studies using mouse B cells in which the artificial receptor was unable to act as a transmembrane signaling element. From these studies, we conclude that B cells express clonally unrestricted, presumably low-avidity, endogenous receptor for POL, and that signaling through this receptor activates B cell differentiation but not cell proliferation.