Peripheral CD19^hi B cells exhibit activated phenotype and functionality in promoting IgG and IgM production in human autoimmune diseases.

ABSTRACT: 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.

SUBMITTER: Liu Z 

PROVIDER: S-EPMC5655037 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature