THE ACTIVATION OF SILENT CLONES AND THE IDIOTYPE REGULATION OF THE GROWTH OF ABPC48 PLASMACYTOMA CELLS.
Item
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Title
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THE ACTIVATION OF SILENT CLONES AND THE IDIOTYPE REGULATION OF THE GROWTH OF ABPC48 PLASMACYTOMA CELLS.
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Identifier
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AAI8601690
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identifier
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8601690
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Creator
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RUBINSTEIN, LEONARD JAY.
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Contributor
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Constantin A . Bona
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Date
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1985
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Language
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English
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Publisher
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City University of New York.
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Subject
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Health Sciences, Immunology
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Abstract
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The treatment of newborn BALB/c mice with minute amounts of either the A48 myeloma protein or monoclonal proteins that express A48 idiotopes, followed by immunization with bacterial levan 2-4 weeks later, elicits an anti-levan response that is dominated by the A48Id. The expansion of A48Id('+) B cell clones in these mice is associated with an increase in A48Id-specific helper T cells. The passive influx of maternal idiotypes into the fetus also exerted profound effects on the development of the immune repertoire. Antibodies displaying a particular idiotype can indirectly expand clones expressing the corresponding idiotype by first stimulating idiotype-specific helper T cells. The study of genetic control of the expression of the A48Id has clearly shown that its expression is not dependent upon MHC or IghC gene complexes in newborn mice treated with either anti-A48, A48, or hyperimmunized with anti-A48-KLH conjugates. However, the activation of U10Id B cell clones through in utero exposure to UPCl0 myeloma protein, is dependent on IghV('a) genes. The neonatal administration of anti-A48 antibodies causes a long-lasting activation of A48Id('+) bearing clones which is related to a direct interaction of the anti-A48Id antibodies and the immune receptor of B cell clones that are A48Id('+). The maturation of these precursors requires challenge by antigen, but antigenic challenge can be replaced by a monoclonal anti-A48Id antibody, thereby representing a homobody, and carrying the internal image of the antigen. The effect of antigen, activation of normal A48Id('+) B cell clones, and monoclonal antibodies sharing A48-UPC10 regulatory idiotopes on the in vivo growth of ABPC48 myeloma cells was also examined. Immunogenic doses of bacterial levan have no detectable effects, whereas tolerogenic doses substantially delay the growth of the myeloma. The activation of normal A48Id('+)B cell clones also has no apparent effect on the growth of the ABPC48 myeloma cells. Among a panel of 15 monoclonal antibodies expressing A48-UPC10 regulatory idiotopes, and expressing V(,H) genes derived from the V(,H)441-4 germ line gene family, 5 were able to provide a long lasting, but not definitive idiotype specific protection against the ABPC48 myeloma cells.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
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Program
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Biomedical Sciences
