Peripheral CD19 hi B cells exhibit activated phenotype and functionality in promoting IgG and IgM production in human autoimmune diseases
SCIENTIFIC REPORTS(2017)
摘要
Systemic Lupus Erythematosus (SLE) and pemphigus are two representative autoimmune diseases driven by pathogenic autoantibody systemically and organ-specifically, respectively. Given the involvement of antibody in the pathogenesis, B cells are inclined to differentiate and function in an abnormal activation model. Here we defined a unique CD19 hi B cell population existing in the periphery of SLE and pemphigus patients as well as in human tonsils. CD19 hi B cells could be induced in vitro after co-culturing fully activated CD4 + T cells with autologous B cells. They expressed high levels of HLA-DR, IgG, IgM and multiple ligands of costimulatory molecules with the capacity to produce extra IgG and IgM. Transcirptome assay revealed that genes involved in B-cell activation and differentiation were up-regulated in CD19 hi B cells. Antibody blockade experiments showed that the interactions between costimulatory molecules contributed to CD19 hi B-cell generation and IgG/IgM production. What is more, frequencies of peripheral CD19 hi B cells from SLE and pemphigus patients were correlated with serum total IgG and IgM, but not with autoantigen-specific antibodies and disease severity. Therefore, our investigation demonstrates that CD19 hi B cells might contain B cell precursors for terminal differentiation and contribute to total IgG/IgM production in human autoimmune diseases.
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关键词
Autoimmune diseases,Systemic lupus erythematosus,Science,Humanities and Social Sciences,multidisciplinary
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