B7-1/2 (CD80/CD86) Direct Signaling to B Cells Enhances IgG Secretion

Abstract

B cell responses are regulated by Ag recognition, costimulatory signals provided by interaction with helper T cells, and by innate signals. We recently provided evidence for a link between the effects of innate and costimulatory signals on B cells during influenza virus infection, by demonstrating that most B cells in the regional lymph nodes of the respiratory tract enhance surface expression of the costimulator B7-2 (CD86) within 24–48 h following infection via a type I IFNR-dependent mechanisms, a finding we are confirming here. While the role of B7-1/2 for helper T cell activation is well documented, its role in direct B cell regulation is poorly understood. Here, our in vivo studies with mixed bone marrow irradiation chimeric mice, lacking B7-1/2 only on B cells, demonstrated that B7-1/2 expression is crucial for induction of maximal local, but to a lesser extent systemic, IgG Ab responses following influenza virus infection. In contrast to mice that completely lack B7-1/2 expression, loss of B7-1/2 on B cells alone did not significantly affect germinal center formation or the extent of CD4+ T cell activation and IFN-γ secretion. Instead, our in vitro studies identify a dramatic effect of B7-2 engagement on IgG, but not IgM secretion by already class-switched B cells. Concomitantly, B7-2 engagement induced expression of X-box binding protein 1 (XBP-1) and spliced XBP1, evidence for increased protein synthesis by these cells. Taken together, these results identify direct signaling through B7-1/2 as a potent regulator of IgG secretion by previously activated B cells.

Single and Coexpression of CXCR4 and CXCR5 Identifies CD4 T Helper Cells in Distinct Lymph Node Niches during Influenza Virus Infection

“…7B). However, IL-4 expression levels overall were very low, consistent with a predominant switch of B cells to IgG2a/c but not IgG1 after influenza virus infection (36). Together, the data show X5 ϩ /X4 ϩ -expressing T GC to be most closely associated with the functions and phenotypes thought to characterize their functions.…”

“…B cell proliferation. Magnetically activated cell sorting (MACS)-enriched, CFSE-labeled B cells at 6.25 ϫ 10 6 cells/ml were pulsed with 1,000 HAU/ml influenza virus A/Mem/71 in culture medium (36) for 3 h at 37°C. A total of 2.5 ϫ 10 5 pulsed B cells were cocultured in 96-well roundbottom plates for 4 days with graded numbers of purified CD4 T cell subsets from MedLN of infected mice in triplicates.…”

Effect of Immunosuppressive Drugs on Humoral Allosensitization after Kidney Transplant

“…84 CTLA4-Ig binds to CD80/ CD86 molecules on dendritic cells and promotes the induction of the immunomodulatory enzyme indoleamine 2,3 dioxygenase 85,86 and the tolerogenic molecule HLA-G. 87 Experimental data suggest that reverse signaling of CD80/ CD86 also exists in B cells. 88,89 It is, therefore, tempting to speculate that, when belatacept binds to CD80/CD86, it directly influences the B cell fate. This mechanism could account for the recent observation that the frequency and absolute number of CD19…”

TLR4- and TRIF-dependent stimulation of B lymphocytes by peptide liposomes enables T cell–independent isotype switch in mice

“…on May 13, 2018. by guest www.bloodjournal.org From CD40L interactions have been reported important for GC formation and class switching. [14][15][16] We found that immunization with A␤1-15 liposomes induced strong anti-A␤ IgM and IgG responses both in the CD28-and CD40L-deficient mice ( Figure 3A-B). Again, predominance of IgG2b and TI-associated IgG3 similar to that observed in WT mice ( Figure 3C-E).…”