B-Cell Superantigens: Molecular and Cellular Implications

Silverman, Gregg J.; Jv, Nayak; Cava, Antonio La

doi:10.3109/08830189709116520

Cited by 12 publications

(8 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Second, the reactivity of the BCR with alleged (auto)antigens could primarily be a function of the V H gene, with some contribution from the HCDR3. Such reactivities occur for classical antigens (183) and autoantigens (184), as well as superantigens (185). This might also explain a potential role of certain viruses [e.g., HTLV-1 (186)(187)(188)(189)] that express structures with superantigenlike features.…”

Section: Clonal Evolution Of Preleukemic Cellsmentioning

confidence: 96%

B Cell Chronic Lymphocytic Leukemia: Lessons Learned from Studies of the B Cell Antigen Receptor

Chiorazzi

Ferrarini

2003

Annu. Rev. Immunol.

332

312

View full text Add to dashboard Cite

B cell chronic lymphocytic leukemia (B-CLL) is an accumulative disease of slowly proliferating CD5(+) B lymphocytes that develops in the aging population. Whereas some patients with B-CLL have an indolent course and die after many years from unrelated causes, others progress very rapidly and succumb within a few years from this currently incurable leukemia. Over the past decade studies of the structure and function of the B cell antigen receptor (BCR) used by these leukemic cells have helped redefine the nature of this disease. In this review we summarize and reinterpret several aspects of these BCR-related studies and how they might relate to the disease. In particular, we address the ability of antigens to select out and drive B cell clones from the normal state to overt leukemic cells by binding to BCRs that are relatively unique and characteristic of B-CLL cells. The differential capacity of some B-CLL cases to continue to transduce signals through the BCR during the leukemic phase and the consequences for the in vivo biology of the leukemic clone is also considered. Finally, we discuss current and emerging views of the cellular origin of B-CLL cells and the differentiation pathways down which we believe these cells progress.

show abstract

Section: Clonal Evolution Of Preleukemic Cellsmentioning

confidence: 96%

B Cell Chronic Lymphocytic Leukemia: Lessons Learned from Studies of the B Cell Antigen Receptor

Chiorazzi

Ferrarini

2003

Annu. Rev. Immunol.

332

312

View full text Add to dashboard Cite

show abstract

“…4 and 5 indicate that clonal expansion is neither associated with usage of a certain V H gene nor diversification of the Ab repertoire. Lack of a V H -associated SAg effect is not surprising because B cell SAgs are so far known to target FR3 of members of certain V H families, typically V H 3 (6,71). Because all swine V H genes belong to the VH3 family and are Ͼ96% homologous (72), a classical B cell SAg would go undetected.…”

Section: Discussionmentioning

confidence: 99%

“…A few viruses elaborate T cell superantigens (SAgs) 3 that expand T cell subpopulations independent of virus specificity that can result in cytokine shock and cause clonal deletion (4,5). Some viruses elaborate B cell SAgs that expand nonvirus-specific B cell subsets (6). This effect may explain why lymphocytic choriomeningitis virus and other viruses evoke polyclonal B cell activation that can result in autoantibodies (7)(8)(9)(10)(11).…”

mentioning

confidence: 99%

Antibody Repertoire Development in Fetal and Neonatal Piglets: XIX. Undiversified B Cells with Hydrophobic HCDR3s Preferentially Proliferate in the Porcine Reproductive and Respiratory Syndrome

Butler

Lemke

Weber

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

Porcine respiratory and reproductive syndrome virus (PRRSV) causes an extraordinary increase in the proportion of B cells resulting in lymphoid hyperplasia, hypergammaglobulinemia, and autoimmunity in neonatal piglets. Spectratypic analysis of B cells from neonatal isolator piglets show a non-Gaussian pattern with preferential expansion of clones bearing certain H chain third complementary region (HCDR3) lengths. However, only in PRRSV-infected isolator piglets was nearly the identical spectratype observed for all lymphoid tissues. This result suggests dissemination of the same dominant B cell clones throughout the body. B cell expansion in PRRS was not associated with preferential VH gene usage or repertoire diversification and these cells appeared to bear a naive phenotype. The B cell population observed during infection comprised those with hydrophobic HCDR3s, especially sequences encoded by reading frame 3 of DHA that generates the AMVLV motif. Thus, the hydropathicity profile of B cells after infection was skewed to favor those with hydrophobic binding sites, whereas the normally dominant region of the hydropathicity profile containing neutral HCDR3s was absent. We believe that the hypergammaglobulinemia results from the products of these cells. We speculate that PRRSV infection generates a product that engages the BCR of naive B cells, displaying the AMVLV and similar motifs in HCDR3 and resulting in their T-independent proliferation without repertoire diversification.

show abstract

“…for a conventional B cell superantigen (BSAg) effect (28,29). In all newborn piglets, V H A expressed with IgM and IgG comprises 25-35% of total V H usage (Table III), but "other V H " contributes up to 45% in PIPs (6,27).…”

Section: Hydrophobic Hcdr3s In Pips Are Especially Expressed With Vhzmentioning

confidence: 99%

Porcine Reproductive and Respiratory Syndrome Virus Subverts Repertoire Development by Proliferation of Germline-Encoded B Cells of All Isotypes Bearing Hydrophobic Heavy Chain CDR3

Butler

Wertz

Weber

et al. 2008

The Journal of Immunology

View full text Add to dashboard Cite

Isolator piglets infected with porcine reproductive and respiratory syndrome virus (PRRSV), which is related to the lactate dehydrogenase-elevating virus of mice, develop severe hypergammaglobulinemia, lymph node adenopathy, and autoimmune disease. Many of the polyclonally activated B cell clones bear hydrophobic H chain CDR3s (HCDR3s) and are disseminated to most lymphoid tissues. We show in this study that B cells with identical hydrophobic HCDR3s are expressed with all major isotypes in PRRSV-infected piglets (PIPs), explaining why PRRSV-induced hypergammaglobulinemia is seen in all major isotypes. Up to one-third of randomly selected VDJ clones from the respiratory tract of PIPs have hydrophobic HCDR3s exclusively bearing VDJ rearrangements with CDR1, CDR2, and nearly intact DH segments in germline configuration. These HCDR3s are long and DHA and DHB are exclusively used in reading frame 3. A minimal tripeptide motif containing three hydrophobic amino acids (Leu, Val, and Ile) or any two plus alanine is common to this hydrophobic patch. We propose that PRRSV infection causes generalized Ag-independent B cell activation and hypergammaglobulinemia with biased expansion of a subpopulation of the preimmune repertoire with hydrophobic binding sites that normally disappears during Ag-driven repertoire diversification. Elevated Ig levels in PIP cannot be explained as antiviral Abs; some Igs can account for autoantibodies to dsDNA and Golgi, whereas those with hydrophobic binding sites may account for the Ig aggregates seen in PIPs and lactate dehydrogenase-elevating virus-infected mice. This diversion from normal repertoire development may explain the delayed immune response to PRRSV.

show abstract

B-Cell Superantigens: Molecular and Cellular Implications

Cited by 12 publications

References 102 publications

B Cell Chronic Lymphocytic Leukemia: Lessons Learned from Studies of the B Cell Antigen Receptor

B Cell Chronic Lymphocytic Leukemia: Lessons Learned from Studies of the B Cell Antigen Receptor

Antibody Repertoire Development in Fetal and Neonatal Piglets: XIX. Undiversified B Cells with Hydrophobic HCDR3s Preferentially Proliferate in the Porcine Reproductive and Respiratory Syndrome

Porcine Reproductive and Respiratory Syndrome Virus Subverts Repertoire Development by Proliferation of Germline-Encoded B Cells of All Isotypes Bearing Hydrophobic Heavy Chain CDR3

Contact Info

Product

Resources

About