The levan-ABPC48 idiotype system: Functional and structural aspects.
Item
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Title
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The levan-ABPC48 idiotype system: Functional and structural aspects.
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Identifier
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AAI9000017
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identifier
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9000017
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Creator
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Bonilla, Francisco Antonio.
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Contributor
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Adviser: Constantin A. Bona
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Date
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1989
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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 | Biology, Microbiology | Biology, Molecular
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Abstract
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The BALB/c myeloma protein ABPC48 (A48) binds bacterial levan (BL) polysaccharide. Its idiotype, designated the A48Id, is expressed by {dollar}<{dollar}10% of normal BALB/c anti-BL antibodies, and 90% or more of those from mice treated with syngeneic polyclonal anti-A48Id.;Hybridomas secreting A48Id{dollar}\sp+{dollar} antibodies were prepared from BALB/c mice injected at birth with syngeneic anti-A48Id, or adults hyperimmunized with anti-A48Id-KLH conjugates, both groups challenged with BL subsequent to anti-Id. Monoclonal antibodies (mAbs) derived from newborn mice bind levan, and interact weakly with the monoclonal anti-A48Id antibody IDA10. MAbs from adults have antigen binding different from A48, and bind IDA10 strongly. Molecular analyses show that 60% of mAbs from young mice, and 80-100% of mAbs from adults express V{dollar}\sb{lcub}\rm H{rcub}{dollar}X24 and V{dollar}\sb{lcub}\rm K{rcub}{dollar}10 genes, as does A48. These findings suggest antigen-driven clonal expansion in young mice versus Id-specific expansion in adults.;Another group of hybridomas was obtained from BALB/c mice either untreated or treated at birth with A48 or IDA10. Spleen cells were cultured in vitro with B cell mitogens, fused, and hybridomas selected for expression of V{dollar}\sb{lcub}\rm H{rcub}{dollar}X24 genes. Forty percent of these mAbs express a V{dollar}\sb{lcub}\rm K{rcub}{dollar}1 gene. This frequency suggests antigen-independent selection affecting the available antibody repertoire.;These mAbs displayed several patterns of binding to polysaccharide-containing antigens. One mAb, and the BALB/c galactan-binding myeloma protein XRPC44, (both expressing V{dollar}\sb{lcub}\rm K{rcub}{dollar}4) bind to galactan and rye levan.;Idiotopes associated with V{dollar}\sb{lcub}\rm H{rcub}{dollar}X24{dollar}\sp+{dollar} antibodies, particularly that defined by IDA10, were expressed. Novel V{dollar}\sb{lcub}\rm H{rcub}{dollar}-V{dollar}\sb{lcub}\rm K{rcub}{dollar} combinations encoded these idiotopes. In mAbs derived from IDA10-treated mice, the IDA10 idiotope appeared at higher frequency, suggesting that mitogens may substitute for antigen in cooperation with anti-Id in clonal expansion. Nucleotide sequences show that the IDA10-defined idiotope can be germline-encoded. Thus, IDA10 may influence clonal selection from the virgin B cell repertoire.
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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.
