IMMUNOCHEMICAL, CELLULAR AND MOLECULAR ASPECTS OF RHEUMATOID FACTORS AND OTHER AUTOANTIBODIES.
Item
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Title
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IMMUNOCHEMICAL, CELLULAR AND MOLECULAR ASPECTS OF RHEUMATOID FACTORS AND OTHER AUTOANTIBODIES.
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Identifier
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AAI8629712
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identifier
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8629712
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Creator
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MANHEIMER-LORY, AUDREY JILL.
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Contributor
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Constantin A . Bona
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Date
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1986
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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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Biology, Microbiology
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Abstract
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The nature of the immune response to polysaccharide thymus-independent (TI) antigens was investigated in rheumatoid factor (RF) producing mouse strains, 129/Sv and MRL/lpr, and their normal congenic counterparts, 129/J and MRL +/+. An age-dependent variation of clones specific for bacterial levan (BL) and alpha l, 3 dextran B1355 (Dex) was observed in 129/J mice. The anti-BL and anti-Dex responses observed for 1-month-old 129/Sv mice far exceeded those of their age-matched controls indicating an accelerated ontogenic development of these immune responses. A poor response was observed for both MRL+/+ and MRL/lpr mice after immunization with BL. MRL mice were unresponsive to Dex. These mice, however, could respond to the T-dependent (TD) form of this antigen, suggesting that perhaps these mice lack a subset of B cells required to respond to TI-2 antigens. The most striking observation was the occurrence of isotype-specific RF subsequent to immunization with these antigens in animals prone to develop RF, as well as in aged animals that do not spontaneously produce RF.;The secondary immune response to TNP-KLH and the anti-immunoglobulin response were studied in 1-, 3- and 6-month old 129/J, 129/Sv MRL+/+ and MRL/lpr mice. A profound inability of aging 129/Sv mice and MRL/lpr mice to produce IgG(,2a) (129/Sv) and all IgG (MRL/lpr) anti-TNP antibodies was observed. This markedly low responsiveness could not be related to the presence of RF since their normal counterparts also produced RF after immunization.;We investigated the immunochemical and molecular characteristics of murine monoclonal RF and other autoantibodies. Although the specificities of these autoantibodies varied, many expressed an interstrain cross-reactive idiotype (IdX). Our panel utilizes a restricted set of the V(,H) repertoire representing the more 3' V(,H) families (V(,H) 7183, V(,H) Q52, V(,H) J558). The nucleotide sequences of two cloned RF V(,H) genes show no major differences between V(,H) genes encoding the heavy chain of autoantibodies and antibodies against foreign antigens. Finally, 60% hybridomas produced from BALB/c, NZB, or MRL/lpr which express V(,H) 7183 genes, are specific for self-epitopes and express IdXs.
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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
