Regulation of an idiotype+ B cell lymphoma. Effects of antigen and anti-idiotopic antibodies on proliferation and Ig secretion.
The B cell surface Ig molecule plays an important regulatory role in delivering inductive/tolerogenic signals to the cell. In this paper, the effect of Ag and anti-idiotopic antibodies on the in vitro proliferation and Ig secretion of a B cell tumor was studied. The tumor (BCL1), which had been transfected with the TEPC-15 VH and VL Ig genes, expresses surface Ig and secretes antibody that binds the hapten phosphorylcholine. We found that Ag (C polysaccharide and phosphorylcholine carrier Ag) and two different anti-idiotopic antibodies, in the absence of T cells, all inhibited the proliferation of the T15+ transfectant cell line. The anti-idiotopic antibodies, but not Ag, also inhibited the secretion of T15 Ig by this cell line, suggesting different functional roles for Ag vs anti-Id in the regulation of B cell inactivation. The inhibition of secretion and proliferation appears to be cell cycle phase related. In addition, mouse rIL-4 could override the inhibition of proliferation induced in these studies. These phenomena, demonstrating that binding of surface Ig can result in the transduction of negative growth signals to a B cell tumor, can be viewed as a manifestation of immunologic tolerance. These findings collectively demonstrate that Ag and anti-Id mediate different signals to B cells via interaction with the surface Ig. Because of the monoclonal nature of the T15 transfectant and the anti-idiotypic antibodies, this system can be used to investigate the underlying molecular reactions involved in the B cell response and induction of tolerance.
Ward
R E
RE
Department of Molecular Immunology, Roswell Park Memorial Institute, Buffalo, NY 14263.
McNamara-Ward
M
M
Webb
C F
CF
Altman
D
D
Lim
P L
PL
Tucker
P W
PW
Kohler
H
H
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology*; D001402:B-Lymphocytes / Q000145:classification / Q000276:immunology*; D002460:Cell Line; D002794:Choline / Q000031:analogs & derivatives*; D007130:Immunoglobulin Idiotypes; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000502:physiology; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000276:immunology*; D051379:Mice; D009194:Myeloma Proteins / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D010641:Phenotype; D010767:Phosphorylcholine / Q000276:immunology* / Q000494:pharmacology; D011135:Polysaccharides, Bacterial / Q000276:immunology* / Q000494:pharmacology; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D014162:Transfection
D000888:Antibodies, Anti-Idiotypic; D007130:Immunoglobulin Idiotypes; D007166:Immunosuppressive Agents; D007378:Interleukins; D009194:Myeloma Proteins; D011135:Polysaccharides, Bacterial; D011947:Receptors, Antigen, B-Cell; C043925:myeloma protein TEPC15; C027158:polysaccharide C-substance (Streptococcus); D010767:Phosphorylcholine; D015847:Interleukin-4; D002794:Choline