Tumor dormancy and cell signaling. II. Antibody as an agonist in inducing dormancy of a B cell lymphoma in SCID mice.
Tumor dormancy can be induced in a murine B cell lymphoma (BCL1) by immunizing BALB/c mice with the tumor immunoglobulin (Ig) before tumor cell challenge. In this report, we have investigated the immunological and cellular mechanisms underlying the induction of dormancy. BCL1 tumor cells were injected into SCID mice passively immunized with antibody against different epitopes on IgM or IgD with or without idiotype (Id)-immune T lymphocytes. Results indicate that antibody to IgM is sufficient to induce a state of dormancy. Antibodies against other cell surface molecules including IgD and CD44 (Pgp1) had no effect on tumor growth. Id-immune T cells by themselves also had no effect on tumor growth in SCID mice. However, simultaneous transfer of anti-Id and Id-immune T cells enhanced both the induction and duration of the dormant state. In vitro studies indicated that antibody to IgM induced apoptosis within several hours and cell cycle arrest by 24 h. Hyper cross-linking increased apoptosis. The Fc gamma RII receptor played little or no role in the negative signaling. Antibodies that did not negatively signal in vitro did not induce dormancy in vivo. The results suggest that anti-IgM plays a decisive role in inducing tumor dormancy to BCL1 by acting as an agonist of IgM-mediated signal transduction pathways.
Racila
E
E
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Scheuermann
R H
RH
Picker
L J
LJ
Yefenof
E
E
Tucker
T
T
Chang
W
W
Marches
R
R
Street
N E
NE
Vitetta
E S
ES
Uhr
J W
JW
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000276:immunology*; D017209:Apoptosis; D002453:Cell Cycle; D002470:Cell Survival; D000939:Epitopes / Q000276:immunology; D007116:Immunization, Passive; D007072:Immunoglobulin D / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D016219:Immunotherapy, Adoptive; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000276:immunology*; D009368:Neoplasm Transplantation; D011961:Receptors, Fc / Q000819:agonists*; D015398:Signal Transduction / Q000502:physiology*; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000939:Epitopes; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D009363:Neoplasm Proteins; D011961:Receptors, Fc; C039951:anti-IgD; C044203:anti-IgM; C035311:immunoglobulin M receptor