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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The large VH3 family of human immunoglobulin genes is commonly used throughout B cell ontogeny. However, B cells of the fetus and certain autoantibody-producing clones are restricted to a recurrent subset of VH3 genes, and VH3 B cells are deficient in certain immunodeficiency diseases. In this study, we have sequenced a set of rearranged VH3 genes generated by genomic polymerase chain reaction (PCR) from normal adults and those with common variable immunodeficiency (CVI). In both groups, all cones were readily identifiable with the fetal VH3 subset, and were further distinguished by limited DH motifs and exclusive use of JH4. In CVI, the residual population of VH3 B cells were notable for predominant use of 56p1-like VH genes. All clones displayed sequence divergence (including somatic mutation) with evidence of strong selection against complementarity-determining region (CDR) coding change. A survey of other V gene families indicates that human V gene diversity may be restricted in general by germline mechanisms. These findings suggest that the expressed antibody repertoire in the human adult may be much smaller than anticipated, and selected by processes in part distinct from the paradigm of maximal antigen-binding diversity.
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PMID:Restricted use of fetal VH3 immunoglobulin genes by unselected B cells in the adult. Predominance of 56p1-like VH genes in common variable immunodeficiency. 156 82

The Cryptococcus neoformans capsular polysaccharide glucuronoxylomannan (GXM) has been conjugated to tetanus toxoid (GXM-TT) as an investigational vaccine. GXM-TT elicits antibodies that are protective in C. neoformans-infected mice. In an effort to characterize the fine specificity and molecular structure of human GXM-TT-elicited antibodies, we generated two GXM monoclonal antibodies (MAbs) from peripheral blood lymphocytes of a volunteer GXM-TT recipient and studied serum GXM antibody idiotype expression in 10 additional vaccinees. The MAbs, 2E9 and 3B6, are the immunoglobulin M(lambda) isotype and bind capsular polysaccharides of C. neoformans serotypes other than the serotype A that was used for immunization. Neither antibody competes with murine GXM MAbs for antigen binding, suggesting that the human MAbs recognize a different epitope. The B-cell superantigen staphylococcal protein A binds both MAbs, and human immunodeficiency virus gp120 binds 2E9. MAb nucleic acid sequence analysis revealed that both antibodies use an identical V lambda 1a-J lambda genetic element with different, somatically mutated, members of the VH3 gene family and different DH and JH gene elements. The gene elements used by both MAbs occur in fetal B-lymphocyte repertoires, autoantibodies, and other polysaccharide antibodies. Post-GXM-TT vaccination GXM antibodies from 10 additional vaccinees expressed a shared idiotype defined by rabbit antiserum raised against MAb 2E9. Our data suggest that the human GXM antibody response is restricted and raise questions regarding the importance of specific variable-region elements and superantigens in the generation of human antibody responses to encapsulated pathogens.
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PMID:Analysis of human monoclonal antibodies elicited by vaccination with a Cryptococcus neoformans glucuronoxylomannan capsular polysaccharide vaccine. 762 23

Infection with human immunodeficiency virus-type 1 (HIV-1) depletes T cells expressing CD4 and B cells expressing immunoglobulin (Ig) VH3 gene products. A subpopulation of normal B cells from non-HIV-infected individuals was shown to bind to HIV gp120 by means of membrane Ig; most of these B cells expressed VH3 family Ig. Serum VH3 IgM from uninfected individuals also avidly bound gp120. Finally, gp120 selectively induced Ig secretion by VH3 B cells, indicating that the binding of gp120 functionally activated these cells. These results indicate that naturally occurring VH3 Ig is a second ligand for gp120 and a candidate superantigen for VH3 B cells.
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PMID:Immunoglobulin VH3 gene products: natural ligands for HIV gp120. 769 Apr 97

Patients undergoing bone marrow transplantation are humorally immunodeficient for one or more years post-transplant. This immunodeficiency could be partially caused by B cell repertoire restriction similar to that observed in ontogeny. To test this idea, the abundance of rearranged genomic segments bearing five variable heavy chain (VH) genes was compared in patients at several timepoints post-transplant and in immunologically normal neonates, infants and adults. The genes evaluated in the study (VH6, VH4-58p2, VH3-56p1, VH3-20p1 and VH3-13-2) were selected from those commonly utilized by fetal B cells. The assay employed quantitative PCR and oligonucleotide hybridization detection under conditions designed to detect relatively unmutated forms of these genes. In blood B cells from early post-transplant (2-5 months) patients, these VH genes were markedly overutilized compared with normal adults. B cells from late post-transplant (6-21 months) patients and from normal neonates and infants also overutilized these genes; however, to a lesser degree than early post-transplant B cells. The data suggest that, as in ontogeny, the B cell repertoire is strikingly restricted to fetal-type VH genes early post-transplant, and may become normal only very late (years) post-transplant.
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PMID:Abundance of a restricted fetal B cell repertoire in marrow transplant recipients. 788 12

The abnormalities of B lymphocytes in human immunodeficiency virus (HIV) infection usually have been attributed to secondary consequences of disturbed immunoregulation. However, recent work has revealed avid binding of HIV gp120 to a conserved immunoglobulin motif unique to the VH3 gene family and the selective gp120-induced activation of VH3 B cells in vitro. This cross-sectional clinical study tests whether HIV infection is associated with a selective response of VH3 B cells in vivo. Levels of blood B cells and serum immunoglobulins (Ig) expressing the D12 idiotope of the VH3 gene family were measured in subjects of the Multicenter AIDS Cohort Study grouped according to clinical stages of HIV infection. A 3-fold elevation in D12 B cells was observed in HIV seropositive versus seronegative groups. This was selective for the D12 population, since total B cell numbers were identical in the two groups. The levels of D12 B cells and CD4 T cells were significantly correlated, and D12 B cells were markedly reduced in the AIDS group (4- and 10-fold, compared to the seronegative and seropositive groups). Analogous differences were also seen in the levels of serum anti-gp120 D12 Ig. This change in VH3 B cells among groups of HIV-infected individuals provides further evidence identifying gp120 as a VH3 B cell superantigen.
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PMID:Effects of HIV infection on VH3 (D12 idiotope) B cells in vivo. 820 42

Human antibody variable region gene usage during human immunodeficiency virus type 1 (HIV-1) infection is examined in the following review, and several hypotheses are presented to account for the distinct patterns of antibody gene expression associated with infection. Evidence supporting qualitatively biased antibody gene expression has been derived from analysis of the human humoral immune response by isoelectric focusing (IEF) and serological and molecular studies of immunoglobulin (Ig) from different lymphoid compartments of HIV-1-infected patients. Preferential usage of heavy-chain variable region (VH) gene families 1 and 4 is supported by serological studies of serum Ig and molecular characterization of anti-HIV-1 human monoclonal antibodies derived from infected patients. Negative biases against VH3 family gene usage are detected by polymerase chain reaction (PCR) studies of peripheral blood lymphocytes from AIDS patients but not by combinatorial phage display library techniques. Biased antibody gene usage and expression during HIV-1 infection may be related to HIV-1 pathogenesis by limiting the available HIV-1 neutralizing repertoire. Further molecular characterization of anti-HIV-1 antibodies and in vivo expression of V-region genes during HIV-1 infection should provide important information regarding antibody gene expression and its relationship to HIV-1 pathogenesis.
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PMID:Human antibody variable region gene usage in HIV-1 infection. 852 30

Many recipients of bone marrow transplant (BMT) make normal amounts of serum immunoglobulin but are deficient in generating specific antibody responses to exogenous stimuli. To determine if abnormal usage of VH genes contributes to this immunodeficiency, the usage of VH genes was determined in peripheral blood B cells of four BMT recipients, two of whom had developed chronic graft versus host disease. The pattern of usage of VH3 or VH4 genes assessed at either 90 days or approximately 1 year after transplant was similar to that observed in healthy subjects and was marked by the over utilization of two elements, one VH3 and one VH4. However, the repertoires of each of the four BMT recipients appeared to be less complex than the repertoires of healthy subjects. The differences were a consequence of the accumulation of somatic mutations among rearrangements in the controls but not in the BMT recipients. The failure to accumulate somatic mutations in rearranged VH genes is consistent with a defect in antigen driven B-cell responses. These results indicate the although the VH gene content of the repertoire has normalized by 90 days posttransplant, a maturational arrest in B-cell differentiation associated with antigen activation persists for at least 1 year after BMT.
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PMID:Immunoglobulin heavy chain variable region gene usage in bone marrow transplant recipients: lack of somatic mutation indicates a maturational arrest. 897 15

The envelope glycoprotein of the human immunodeficiency virus (HIV-1), gp120, has recently been characterized as a novel immunoglobulin superantigen (Ig-SAg) [1,2]. Analogous to the interaction of SAgs with T cells, gp120 binds to an unusually large proportion of immunoglobulins (lgs) from HIV-uninfected individuals; most, if not all of these Igs are members of the VH3 family [3]. Functionally, gp120 preferentially stimulates VH3 B cells in vitro. This stimulation correlates with an in vivo VH3 activation during HIV infection. Curiously, this initial activation is followed by a subsequent depletion of VH3-expressing B cells as individuals progress to AIDS. In this article we will review our current understanding of the superantigenic properties of HIV gp120. Specifically we will focus on structural aspects of the binding interaction. on the ontological development of these superantigen-binding antibodies, and on potential roles that this unconventional Ig-pathogen interaction might play in the pathogenesis of HIV-induced disease.
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PMID:HIV-1 gp120: a novel viral B cell superantigen. 918 84

We examined the IgM VH gene subgroup use-distribution in serial blood samples of 37 human immunodeficiency virus (HIV)-infected patients and a group of HIV-seronegative healthy adults. The IgM VH gene repertoires of healthy adults were relatively similar to one another and were stable over time. In contrast, individuals infected with HIV had IgM VH gene repertoires that were significantly more heterogeneous and unstable. Persons at early stages of HIV infection generally had abnormal expression levels of Ig VH3 genes and frequently displayed marked fluctuations in the relative expression levels of this VH gene subgroup over time. In contrast, persons with established acquired immunodeficiency syndrome (AIDS) had a significantly lower incidence of abnormalities in Ig VH3 expression levels, although continued to display abnormalities and instability in the expression levels of the smaller Ig VH gene subgroups. Moreover, the skewing and/or fluctuations in the expressed-IgM VH gene repertoire appeared greatest for persons at earlier stages of HIV infection. These studies show that persons infected with HIV have aberrant and unstable expression of immunoglobulin genes suggestive of a high degree humoral immune dysregulation and ongoing humoral immune responses to HIV-associated antigens and superantigens.
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PMID:Aberrant and unstable expression of immunoglobulin genes in persons infected with human immunodeficiency virus. 969 20

The importance of humoral immunity for resistance to Cryptococcus neoformans is uncertain. A case-controlled study of the human antibody response to C. neoformans comparing the serum antibody profiles of human immunodeficiency virus (HIV)-infected persons who did (HIV+/CM+) or did not (HIV-infected controls) develop cryptococcal meningitis (CM) and HIV-uninfected persons with samples obtained from the Multicenter AIDS Cohort Study was performed. Total immunoglobulin concentrations were determined, and the specificity, isotype, and idiotype expression of antibodies to C. neoformans capsular glucuronoxylomannan were analyzed by ELISA. Compared with the HIV+/CM+ group, the HIV-infected control group had significantly lower levels of total IgM, IgA, and antibodies expressing a certain VH3 determinant. The HIV-infected control group manifested an increase in immunoglobulin levels with a decrease in CD4 lymphocytes. The findings suggest a possible association between reduced expression of certain immunoglobulin subsets and HIV-associated CM.
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PMID:Quantitative and qualitative differences in the serum antibody profiles of human immunodeficiency virus-infected persons with and without Cryptococcus neoformans meningitis. 1051 12


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