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Open AccessJournal ArticleDOI

Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus.

TLDR
There are profound abnormalities in the various B cell compartments in SLE that respond differently to immunosuppressive therapy, and CD27high plasma cells showed a similar degree of somatic hypermutation, but preferentially employed VH4 family members.
Abstract
In patients with active systemic lupus erythematosus (SLE), a marked B lymphocytopenia was identified that affected CD19(+)/CD27(-) naive B cells more than CD19(+)/CD27(+) memory B cells, leading to a relative predominance of CD27-expressing peripheral B cells CD27(high)/CD38(+)/CD19(dim)/surface Ig(low)/CD20(-)/CD138(+) plasma cells were found at high frequencies in active but not inactive SLE patients Upon immunosuppressive therapy, CD27(high) plasma cells and naive CD27(-) B cells were markedly decreased in the peripheral blood Mutational analysis of V gene rearrangements of individual B cells confirmed that CD27(+) B cells coexpressing IgD were memory B cells preferentially using V(H)3 family members with multiple somatic mutations CD27(high) plasma cells showed a similar degree of somatic hypermutation, but preferentially employed V(H)4 family members These results indicate that there are profound abnormalities in the various B cell compartments in SLE that respond differently to immunosuppressive therapy

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Maintenance of Serological Memory by Polyclonal Activation of Human Memory B Cells

TL;DR: It is shown that human memory B lymphocytes proliferate and differentiate into plasma cells in response to polyclonal stimuli, such as bystander T cell help and CpG DNA, which offers a means to maintain serological memory for a human lifetime.
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Induction of Dendritic Cell Differentiation by IFN-α in Systemic Lupus Erythematosus

TL;DR: The capacity of SLE patients' serum to induce DC differentiation correlated with disease activity and depended on the actions of interferon-α (IFN-α), suggesting unabated induction of DCs by IFN- α may drive the autoimmune response in SLE.
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Competence and competition : the challenge of becoming a long-lived plasma cell

TL;DR: Studies of the biology of plasma cells reveal a mechanism of intriguing simplicity and elegance that focuses memory provided by plasma cells on recently encountered pathogens while minimizing the 'fading' of memory for pathogens encountered in the distant past.
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B cell depletion as a novel treatment for systemic lupus erythematosus: A phase I/II dose-escalation trial of rituximab

TL;DR: Rituximab therapy appears to be safe for the treatment of SLE and holds significant therapeutic promise, at least for the majority of patients experiencing profound B cell depletion.
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New insights into the immunopathogenesis of systemic lupus erythematosus

TL;DR: Improved understanding of the pathogenesis of SLE is driving a renewed interest in targeted therapy, and researchers are now on the verge of developing targeted immunotherapy directed at treating either specific organ system involvement or specific subsets of patients with SLE.
References
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Journal ArticleDOI

The 1982 revised criteria for the classification of systemic lupus erythematosus

TL;DR: The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunologic knowledge and improve disease classification and showed gains in sensitivity and specificity.
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Human Immunoglobulin (Ig)M+IgD+ Peripheral Blood B Cells Expressing the CD27 Cell Surface Antigen Carry Somatically Mutated Variable Region Genes: CD27 as a General Marker for Somatically Mutated (Memory) B Cells

TL;DR: It is reported here that human IgM+IgD+ peripheral blood (PB) B cells expressing the CD27 cell surface antigen carry mutated V genes, in contrast to CD27-negative IgM-only tonsillar germinal center and plasma cells, which may represent a general marker for memory B cells in humans.
Journal ArticleDOI

Cellular Origin of Human B-Cell Lymphomas

TL;DR: The origin of human lymphomas has been studied by various approaches, including histology and immunophenotyping, but sequence analysis of the variable-region genes of B-cell lymphomas offered a molecular approach to studying the origin of the tumors.
Journal ArticleDOI

Analysis of somatic mutation in five B cell subsets of human tonsil.

TL;DR: It is found that the somatic mutation machinery is activated only after B cells reach the germinal center and become centroblasts (Bm3), and the analysis of Ig variable region transcripts from the different subpopulations confirms that the pathway of B cell differentiation from virgin B cell throughout the gerMinal center up to the memory compartment can be traced with phenotypic markers.
Journal ArticleDOI

Identification of Functional Human Splenic Memory B Cells by Expression of CD148 and CD27

TL;DR: Examining the expression of the receptor-type protein tyrosine phosphatase CD148 on human B cells identifies CD148 and CD27 as markers which positively identify memory B cells present in human spleen.
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