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Differential Presentation of Tolerogenic Immunoglobulin In Vivo by Macrophages and by a Lymphoid Dendritic Cell‐Like Tumor Line
Author(s) -
Phipps Richard P.,
Illig Karl,
Schad Victoria,
Bhimani Karim
Publication year - 1988
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.43.3.271
Subject(s) - biology , immunology , in vivo , antibody , macrophage , hapten , antigen presentation , t cell , dendritic cell , microbiology and biotechnology , in vitro , immune system , biochemistry
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 E 2 , 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 × 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.