BACKGROUND The mechanisms underlying tolerance induction and maintenance in autoimmune arthritis remain elusive. In a mouse model of rheumatoid arthritis, collagen type II (CII)-induced arthritis, we explore the contribution of B cells to antigen-specific tolerance. METHODS To generate expression of the CII-peptide specifically on B-cell major histocompatibility complex type II, lentiviral-ba...

The survival of naïve T cells is believed to require signals from TCR-pMHC interactions and cytokines such as IL-7. In contrast, signals that negatively impact naïve T cell survival are less understood. We conducted a forward genetic screening of mice and found a mutant mouse line with reduced number of naïve T cells (T-Red mice). T-Red mice have a point mutation in the Kdelr1 gene, and their n...

Cells expressing the spike (S) glycoprotein of the neurotropic JHM strain (JHMV) of mouse hepatitis virus (MHV) are susceptible to lysis by B cells derived from naïve mice, including B cells from perforin-deficient mice. Cytolysis requires interaction of the virus receptor and the viral S glycoprotein, is independent of other viral-induced components, and is not a unique property of B cells. Ne...

This study examines the loss of peripherally induced B cell immune tolerance in Rheumatoid arthritis (RA) and establishes a novel signaling-based measure of activation in a subset of autoreactive B cells--the Induced tolerance status index (ITSI). Naturally occurring naïve autoreactive B cells can escape the "classical" tolerogenic mechanisms of clonal deletion and receptor editing, but remain ...

The effective accumulation and interaction of mature dendritic cells (DCs) and naïve T cells within lymph nodes (LNs), which are driven by the CCR7-CCL19/CCL21 chemokine axis, are critical for the induction of adaptive T-cell immunity. Human natural killer (NK) cells activated by interleukin (IL)-18 exhibit a unique 'helper' activity in promoting productive DC-T cell interactions, inducing DC m...

A 33-year-old woman underwent unrelated cord blood transplantation (U-CBT) for myelodysplastic syndrome (MDS)-related secondary AML. She showed impressive increases in the number of CD19+ B cells in bone marrow and CD19+27-IgD+ B cells in peripheral blood from about 1 month to 3 months after U-CBT. The serum level of IL-6 temporarily increased after transplantation, and this increase seemed to ...