Hyperresponsive B Cells in CD22-Deficient Mice

O’Keefe, Theresa L.; Williams, Gareth T.; Davies, Sarah L.; Neuberger, Michael S.

doi:10.1126/science.274.5288.798

Cited by 491 publications

(329 citation statements)

References 29 publications

Supporting

Mentioning

309

Contrasting

Order By: Relevance

“…40 Considerable evidence supports the hypothesis that depressed levels of CD22 on B cells can promote IgG ANA production. [41][42][43] In contrast to our results, Grimaldi et al 44 found that mRNA and surface protein expression of Cd22 were upregulated in response to E2 in BALB/c mice and proposed that this upregulation may be involved in the escape of autoreactive B cells from tolerance. Differences in the dose of E2 used or the genetic background of the mice may have contributed to this discordance.…”

Section: Discussioncontrasting

confidence: 99%

Identification of candidate genes that influence sex hormone-dependent disease phenotypes in mouse lupus

2007

View full text Add to dashboard Cite

Ninety percent of systemic lupus erythematosus patients are female, and gender differences in lupus susceptibility are also observed in (New Zealand Black Â New Zealand White)F1 (BWF1) lupus-prone mice. We followed orchiectomized, intact male and female BWF1 mice for lupus-like disease for 1 year. A comparative gene expression analysis was then used to identify candidate genes potentially responsible for gender-dependent differences in lupus susceptibility. Seven genes encoded on the sex chromosomes and 77 probe sets, including 14 immunoglobulin genes, encoded on the autosomal chromosomes were identified as differentially expressed in male versus female BWF1 splenocytes prior to disease onset. Five genes were determined to be regulated by either estradiol or dihydrotestosterone in an in vivo system and most of them were preferentially expressed in antigen-presenting cells. Gender differences in the expression of Csf3-r, Histh1c, Serpinb2, Slc6a4 and Cd22 in BWF1 mice are the result of transcriptional modification by sex hormones and warrant further investigation. The identification of candidate genes and their expression patterns in splenocyte sub-populations provide new information regarding the mechanisms by which sex hormones influence the development of mouse lupus.

show abstract

Section: Discussioncontrasting

confidence: 99%

Identification of candidate genes that influence sex hormone-dependent disease phenotypes in mouse lupus

2007

View full text Add to dashboard Cite

show abstract

“…For CD22-positive B-cell lymphoma, immobilized but not soluble epratuzumab can inhibit cellular proliferation, regardless of crosslinking (Nitschke et al, 1997). CD22 has been observed to negatively regulate signaling (PawlakByczkowska et al, 1989;O'Keefe et al, 1996;Otipoby et al, 1996;Sato et al, 1996), although other studies with human B-lymphoma cells suggest an involvement of CD22 with the BCR that can inhibit proliferation (Nitschke et al, 1997). These and other factors appear to be involved in the activity of epratuzumab in the biologically complex groups of lymphoma and autoimmune diseases.…”

Section: Cd22 As a Target For Immunotherapy In B-cell Malignanciesmentioning

confidence: 99%

Preclinical and clinical evaluation of epratuzumab (anti-CD22 IgG) in B-cell malignancies

Leonard

Goldenberg

2007

Oncogene

View full text Add to dashboard Cite

The vast majority of non-Hodgkin's lymphomas are of B-cell phenotype. Development of unlabeled or radiolabeled therapeutic monoclonal antibodies against the cell surface antigen, CD20, has revolutionized the treatment of these malignancies. It is clear that antibodies targeting other B-cell-specific molecules, such as CD22, also offer potential therapeutic benefit. Epratuzumab is a humanized anti-CD22 monoclonal, which has undergone preclinical and phase I/II clinical evaluation in patients with indolent or aggressive lymphoma. Data suggest that this agent is well tolerated, and can induce tumor regressions. Trials are currently evaluating its safety and activity in combination with rituximab (chimeric anti-CD20) and standard chemotherapy are ongoing. Initial results suggest that these regimens have acceptable toxicity, and that epratuzumab warrants further evaluation as an adjunct to standard lymphoma treatment regimens.

show abstract

“…B cells from mice deficient in Lyn (10)(11)(12), CD22 (13)(14)(15)(16), SHP-1 (17,18) exhibit a hyperreactive phenotype and produce autoantibodies. Indeed, Lyn-deficient mice demonstrate activation of autoreactive B cells and subsequent SLE-like symptoms, such as the production of anti-double-stranded DNA (anti-dsDNA) antibodies, splenomegaly, and glomerulonephritis (11,12).…”

mentioning

confidence: 99%

Association of a four–amino acid residue insertion polymorphism of the HS1 gene with systemic lupus erythematosus: Molecular and functional analysis

Otsuka

Horiuchi

Yoshizawa

et al. 2004

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. To investigate whether polymorphism(s) or mutation(s) in the hematopoietic cellspecific Lyn substrate 1 (HS1) gene are involved in the pathogenesis of systemic lupus erythematosus (SLE).Methods. The entire coding region of the HS1 gene was analyzed by reverse transcriptase-polymerase chain reaction/single-strand conformational polymorphism analysis. HS1-transfected WEHI-231 cells or B lymphocytes from patients with SLE were studied for apoptosis, activation, and proliferation by flow cytometric analysis and MTT assay.Results. We identified a glutamic acid-prolineglutamic acid-proline insertion between codons 366 and 367 (EPEP366-367ins) and 2 amino acid substitutions (A235T and E361K). The genotype frequency among individuals homozygous for the EPEP؉ allele was 0.184 in 201 patients with SLE but only 0.098 in 184 healthy individuals (P ‫؍‬ 0.016). The allele frequency of EPEP366-367ins was 0.408 in patients with SLE; this frequency was significantly higher than that in healthy controls (0.312) (P ‫؍‬ 0.006). WEHI-231 cells transfected with EPEP؉ HS1 were 100-fold more sensitive to B cell receptor (BCR)-mediated apoptosis than were those transfected with HS1 without EPEP. B lymphocytes from SLE patients with the EPEP؉ allele were significantly more apoptotic without BCR stimulation and less activated after BCR stimulation than were those from SLE patients without the EPEP allele. Conclusion. These results suggest that HS1 with the EPEP insertion polymorphism transmits accelerated signals from BCR and is involved in the pathogenesis of SLE.Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease characterized by the presence of a variety of autoantibodies. Various genetic and environmental factors, including B cell hyperactivity, T cell dysfunction, and cytokine dysregulation, initiate immune activation in SLE that culminates in organ inflammation and damage (1-9). It has been considered that B cells are innocent bystanders that are activated secondarily by autoreactive T lymphocytes. However, recent evidence from the study of human SLE and its murine models suggests that B lymphocytes are intrinsically defective and are primarily essential for the maintenance of activated/memory T cells by presenting antigens to T cells.B cells from mice deficient in Lyn (10-12), CD22 (13-16), SHP-1 (17,18) exhibit a hyperreactive phenotype and produce autoantibodies. Indeed, Lyn-deficient mice demonstrate activation of autoreactive B cells and subsequent SLE-like symptoms, such as the production of anti-double-stranded DNA (anti-dsDNA)

show abstract

Hyperresponsive B Cells in CD22-Deficient Mice

Cited by 491 publications

References 29 publications

Identification of candidate genes that influence sex hormone-dependent disease phenotypes in mouse lupus

Identification of candidate genes that influence sex hormone-dependent disease phenotypes in mouse lupus

Preclinical and clinical evaluation of epratuzumab (anti-CD22 IgG) in B-cell malignancies

Association of a four–amino acid residue insertion polymorphism of the HS1 gene with systemic lupus erythematosus: Molecular and functional analysis

Contact Info

Product

Resources

About