A murine model for B-cell lymphomagenesis in immunocompromised hosts: natural killer cells are an important component of host resistance to premalignant B-cell lines.
The accompanying paper (D. W. Felsher et al., Cancer Res., 50:7042-7049, 1990) describes a new panel of cloned murine B-cell lines with a premalignant phenotype and in vivo-derived malignant variants. This paper assesses the contribution of immune mediated antitumor mechanisms which might account for host resistance to the tumorigenicity of these cell lines. Conventional T-cell-dependent responses did not appear to be critical to host resistance. In vivo elimination of T-helper cells with anti-L3T4 monoclonal antibody did not reduce host resistance to the tumorigenicity of these cell lines, nor did these cell lines elicit cytotoxic T-cell activity. However, a strong correlation was found between tumorigenicity and host natural killer (NK) activity. In vitro studies demonstrated that the cell lines were as NK sensitive as the prototypical NK target, YAC-1, whereas the malignant variants fully tumorigenic in normal hosts were greater than 20-fold less NK sensitive than were the parent cell lines. In vivo depletion of NK cells with anti-asialo-GM1 in BALB/c strongly diminished host resistance to cell line tumorigenicity, whereas polydeoxyinosinic-deoxycytidilic acid induction of NK cells enhanced host resistance. These findings indicate that NK function is a critical component to host resistance in this system and suggest that endogenous cellular mechanisms which overcome NK sensitivity could be a target for secondary transforming events in B-cell lymphomagenesis. They also raise the unexpected possibility that a non-antigen-dependent (versus immune cytotoxic T-lymphocytes) effector mechanism may be the key deficit promoting B-cell neoplasia in the setting of immunocompromised states.
Department of Pathology, UCLA School of Medicine 90024.
D W
DW
Felsher
S H
SH
Rhim
J
J
Braun
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007111:Immunity, Cellular / Q000502:physiology; D007121:Immunocompetence / Q000276:immunology*; D007370:Interferon Type I / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000209:etiology* / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology
D007370:Interferon Type I