Differential presentation of tolerogenic immunoglobulin in vivo by macrophages and by a lymphoid dendritic cell-like tumor line.
Previous work indicated that macrophages and a lymphoid dendritic cell-like tumor line, P388AD.2, possessed a differential ability to present a haptenated immunoglobulin (tolerogen) in vitro. Macrophages presented fluorescein-conjugated sheep gamma globulin (FL-SGG) and elicited B-cell unresponsiveness. In contrast, P388AD.2 presented this normally tolerogenic signal as an immunogenic one and induced augmented anti-hapten antibody responses. The objective of the present study was to determine whether differential tolerogen presentation could occur in vivo using defined accessory cells pulsed with FL-SGG. Interestingly, the intravenous (IV) injection of FL-SGG-pulsed thioglycollate-elicited macrophages, which secreted prostaglandin E2, induced hapten-specific B-cell unresponsiveness in syngeneic recipients. One thousand times as much FL-SGG in soluble form was required to produce the same degree of unresponsiveness. In contrast to macrophage-elicited negative signalling, non-prostaglandin secreting P388AD.2, when pulsed with FL-SGG, induced hapten-specific responses 2-3 times control values. Moreover, as few as 2 x 10(4) FL-SGG-pulsed P388AD.2 induced significant augmentation of the anti-FL antibody response. The presentation of FL-SGG in an immunogenic fashion by P388AD.2 was rapid and long lasting since increased responses were demonstrated as early as 1 day or as long as 21 days after IV injection. P388AD.2 were not simply acting as a passive carrier, nor permitting host presentation of FL-SGG, since there were requirements for P388AD.2 viability, and for syngeneic recipients in order to generate augmented anti-FL antibody responses. Moreover, inappropriate presentation of FL-SGG by P388AD.2 injected into allogeneic recipients did not elicit positive or negative signalling. In order to demonstrate that the ability of P388AD.2 to present FL-SGG in an immunogenic fashion was not simply a property of all tumor cells, the P388D1 cell line was pulsed with FL-SGG and injected. Neither tolerance nor augmentation was induced. Overall these results demonstrate that the type of antigen-presenting cell which introduces the immune system to an immunoglobulin tolerogen is critical to the induction of B-cell unresponsiveness or priming.
Phipps
R P
RP
University of Rochester Cancer Center, Immunology Unit, NY 14642.
Illig
K
K
Schad
V
V
Bhimani
K
K
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D007108:Immune Tolerance; D007114:Immunization; D007136:Immunoglobulins / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011453:Prostaglandins / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000276:immunology
D007136:Immunoglobulins; D011453:Prostaglandins