The relationship of the V(K)1 gene family of the immunoglobulin light chain to autoantibody formation in the New Zealand Black mouse.
Item
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Title
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The relationship of the V(K)1 gene family of the immunoglobulin light chain to autoantibody formation in the New Zealand Black mouse.
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Identifier
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AAI9119611
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identifier
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9119611
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Creator
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Bailey, Naila Celesta.
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Contributor
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Adviser: Constantin A. Bona
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Date
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1991
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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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We conduct studies to determine whether there is a linkage between the occurrence of lupus nephritis and autoantibodies with some genes of the immunoglobulin (Ig) gene superfamily, namely, the variable region of the Ig light chain (V{dollar}\sb{lcub}\rm K{rcub}{dollar}) the heavy chain (V{dollar}\sb{lcub}\rm H{rcub}{dollar}), the variable region of the T-cell receptor and the I-A locus of the major histocompatibility complex. Our results on two recombinant inbred strains (RI) NZBx129/J and NZBxSM/J revealed that the V{dollar}\sb{lcub}\rm K{rcub}{dollar}1{dollar}\sp{lcub}\rm b{rcub}{dollar} NZB haplotype was significantly associated with the occurrence of Coombs' autoantibodies.;Restriction fragment length polymorphism (RFLP) analysis of the V{dollar}\sb{lcub}\rm K{rcub}{dollar}1 gene family in NZB mice showed a particular polymorphism that is not seen in non-autoimmune mouse strains. In addition, the V{dollar}\sb{lcub}\rm K{rcub}{dollar}1 light chains are subdivided into five subgroups ({dollar}\rm V\sb K1A-V\sb K1E{dollar}). Amino acid sequencing of myeloma proteins from NZB mice have demonstrated that they belong only to the {dollar}\rm V\sb K{dollar}1B subgroup. No {dollar}\rm V\sb K{dollar}1A gene was present in the serum light chain of NZB or in a screening of over 125 plasmacytomas derived from NZB. It was, therefore, established that the lack of {dollar}\rm V\sb K{dollar}1A expression in NZB is due to either a regulatory mechanism preventing its expression in antibodies, or the absence of this particular subgroup from the germline gene pool of NZB.;We sequenced 10 functional {dollar}\rm V\sb K{dollar}1 germline genes from NZB HindIII digested liver DNA, belonging to {dollar}\rm V\sb K{dollar}1A,B,C,D and a new subgroup designated F. The structure of these genes were similar to the non-autoimmune strain Balb/c, with the exception of a few allelic differences. Several {dollar}\rm V\sb K{dollar}1 germline genes were isolated from a single fragment and identical genes were identified in two different RFLP migrating bands. Therefore, the complexity of the genes encoding the variable region of Igs cannot be determined by RFLP analysis alone.;Sequencing cDNA from NZB hybridomas secreting antibodies with different specificities revealed that they expressed different {dollar}\rm V\sb K{dollar}1 subgroups isolated from NZB at random with no bias towards a particular subgroup, and with no somatic mutations.
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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.
