From Human Autoantibodies to the Fetal Antibody Repertoire to B Cell Malignancy: It's a Small World After All

Chen, Pojen P.; Olsen, Nancy J.; Yang, Pei‐Ling; Soto‐Gil, Rafael W.; Olee, Tsaiwei; Siminovitch, Katherine A.; Carson, Dennis A.

doi:10.3109/08830189009056732

Cited by 33 publications

(24 citation statements)

References 109 publications

(38 reference statements)

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“…This, in turn, may alter the humoral immune response to bacterial and/or viral infection, resulting in the overproduction of aberrant antibodies that contribute to the development and/or perpetuation of autoimmune disorders (29). Alternatively, deletion of hv3005-like genes may confer disease susceptibility through other mechanisms.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, serological analyses of newborn mice showed a high frequency of autoreactive B cells, whose expressed autoantibodies often shared cross-reactive idiotypes (CRIs) (17)(18)(19). Further, molecular analyses of the neonatal antibody repertoire in humans and mice indicated that a restricted set of Vh genes were expressed preferentially, and that such early expressed Vh genes frequently encoded idiotypically related autoantibodies (8,10,13,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Combined, these findings suggested that autoantibodies may serve some important physiological functions of the immune system, by augmenting the opsonization of infectious agents, and the clearance ofimmune complexes and senile cells (reviewed in references 4, 6, 7, 29 and 31).…”

Section: Introductionmentioning

confidence: 99%

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Molecular basis of an autoantibody-associated restriction fragment length polymorphism that confers susceptibility to autoimmune diseases.

Olee¹,

Yang²,

Siminovitch³

et al. 1991

J. Clin. Invest.

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Recently, combined serological and molecular studies ofautoantibodies have revealed that these antibodies play an important role in the normal function of the immune system and in the development of the B cell repertoire. Accordingly, we hypothesized that a homozygous deletion of a critical autoantibody-associated Ig variable (V) gene may alter the immune system and thus predispose the host to autoimmune disorders. Initial experiments revealed several restriction fragment length polymorphisms (RFLP) of the Humhv3005 gene, that is likely to encode heavy chains of rheumatoid factors, and the closely related 1.9111 gene. By probing EcoRl-digested DNA with the Humhv3005/P1 probe, we found that one of the four major hybridizing bands was missing in -20% of patients with either rheumatoid arthritis or systemic lupus erythematosus, but only 2% of normal subjects. To delineate the genetic basis of this polymorphism, we have now employed the PCR to amplify and analyze hv3005, 1.9III, and homologous genes in individuals with characteristic RFLP genotypes. Our results indicate that the human Vh gene repertoire contains several hv3005-and 1.9II-like genes, and that a complete deletion of the hv3005-like genes is relatively restricted to a subset of autoimmune patients. These findings provide initial evidence for deletion of developmentally regulated autoreactive V genes in autoimmune diseases. (J. Clin. Invest. 1991.88:193-203.)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular basis of an autoantibody-associated restriction fragment length polymorphism that confers susceptibility to autoimmune diseases.

Olee¹,

Yang²,

Siminovitch³

et al. 1991

J. Clin. Invest.

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“…In addition to coding for autoantibodies, a restricted Vh gene group might also encode the H chains of antibodies against common environmental pathogens, such as the herpesviruses. In support of this contention, it was shown previously that the EVI-15 anti-cytomegalovirus (CMV) antibody utilized the autoantibody-related Humhv 1051 and Humkv325 genes, the Vh and the VK genes that encode many Wa-positive RFs (8,(21)(22)(23). To examine this hypothesis further, we adapted the anchored polymerase chain reaction (APCR) to clone and analyze rapidly the expressed V genes for three IgG antibodies against herpes simplex virus (HSV) and varicella-zoster virus (VZV), both of the herpes family.…”

mentioning

confidence: 94%

“…During the last 5 years, intensive studies have revealed that many autoantibodies of different specificities recurrently use a small set of Ig V genes (8)(9)(10)(11)(12). For example, Humkv325 encodes the K L chains of several rheumatoid factors (RFs), two antibodies against low-density lipoprotein, one antibody against intermediate filaments, and a few cold agglutinins (8,13); similarly, VH26 encodes the H chains of the 16/6 idiotype-positive anti-DNA antibodies and an IgM antibody that binds to IgG, thyroglobulin, and other antigens (9,10,(14)(15)(16).…”

mentioning

confidence: 99%

“…For example, Humkv325 encodes the K L chains of several rheumatoid factors (RFs), two antibodies against low-density lipoprotein, one antibody against intermediate filaments, and a few cold agglutinins (8,13); similarly, VH26 encodes the H chains of the 16/6 idiotype-positive anti-DNA antibodies and an IgM antibody that binds to IgG, thyroglobulin, and other antigens (9,10,(14)(15)(16). On the other hand, analysis of Vh gene expression during early ontogenic development showed that a small number of Vh genes were expressed frequently (17)(18)(19).…”

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confidence: 99%

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Sequence analyses of three immunoglobulin G anti-virus antibodies reveal their utilization of autoantibody-related immunoglobulin Vh genes, but not V lambda genes.

Huang¹,

Olee²,

Masuho³

et al. 1992

J. Clin. Invest.

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Accumulated sequence analyses of the antibody repertoire have revealed that most autoantibodies and developmentally regulated antibodies share a small set of germline Ig-variable region (V) genes. The findings have prompted speculation that certain autoantibodies are of developmental importance and may be instrumental in maintaining homeostasis of the adult antibody repertoire. In order to evaluate this hypothesis critically, it is first necessary to determine the V gene usage in human antibodies against foreign substances. Unfortunately, only a few such antibodies have had their heavy and light chains characterized. To rectify the situation, we adapted the anchored polymerase chain reaction to clone and analyze rapidly the expressed V genes for three anti-virus IgG antibodies. The results show that all three heavy chain V (Vh) genes are highly homologous to the known autoantibody-related Vh genes. In contrast, two light chain V (VL) genes of the VX1 subgroup are similar to a non-autoantibody-related germline VX1 gene. Taken together with the reported Vh and VL sequences of several antibodies against viruses and bacteria, the data show that many antipathogen antibodies may use the same small set of Vh genes that encode autoantibodies, but diverse VL genes that are distinct from autoantibody-related VL genes. Thus, only a small portion of the potentially functional germline Vh genes are used recurrently to generate most antibodies in a normal antibody repertoire, regardless of their reactivities with either self or non-self. (J. Clin. Invest. 1992. 90:2197-2208 Key words: anchored polymerase chain reaction * antibodies * herpes simplex virus * immunoglobulin V genes * varicella zoster virus

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Generation and Characterization of two Monoclonal Self‐Associating IgG Rheumatoid Factors from a Rheumatoid Synovium

Deftos

Tighe

et al. 1992

Arthritis & Rheumatism

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Objective. To study IgG rheumatoid factor (RF) from rheumatoid synovium.Methods. We fused the K6H6/B5 human-mouse heterohybridoma with unstimulated rheumatoid synovial B cells to generate IgG-RF-secreting hybridomas.Results. The RFs from 2 such hybridomas bound specifically to the Fc fragment of human IgG and self-associated to form immune complexes. Such immune complexes are a major characteristic of the pathogenic IgG-RFs in rheumatoid synovium. Conclusion. IgG-RF-secreting hybridomas have been obtained. Analyses may reveal the underlying mechanisms of the induction of IgG-RF.It has been shown that rheumatoid synovial fluid contains abundant aggregates of IgG and rheumatoid factors (RFs), and depressed levels of complement components (1). These findings suggest that RFs

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From Human Autoantibodies to the Fetal Antibody Repertoire to B Cell Malignancy: It's a Small World After All

Abstract: KEYWORDS: autoantibody, fetal antibody repertoire. antibody netwrk, Ig V genes, B cell malignancyInt Rev Immunol Downloaded from informahealthcare.com by Flinders University of South Australia on 01/08/15For personal use only.

Cited by 33 publications

References 109 publications

Molecular basis of an autoantibody-associated restriction fragment length polymorphism that confers susceptibility to autoimmune diseases.

Molecular basis of an autoantibody-associated restriction fragment length polymorphism that confers susceptibility to autoimmune diseases.

Sequence analyses of three immunoglobulin G anti-virus antibodies reveal their utilization of autoantibody-related immunoglobulin Vh genes, but not V lambda genes.

Generation and Characterization of two Monoclonal Self‐Associating IgG Rheumatoid Factors from a Rheumatoid Synovium

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