SUMMARYTo investigate the role of B cells in the development of CIA, a model for rheumatoid arthritis, we investigated susceptibility to CIA in mice lacking B cells due to the deletion of the IgM heavy chain gene (mMT). The mMT deletion was backcrossed into two different CIA-susceptible strains, B10.Q and B10.RIII. Two different variants of the CIA model are inducible in these strains: in B10.Q with rat type II collagen (CII) and in B10.RIII with bovine CII. Homozygous deletion of the IgM gene led to the absence of B cells and dramatically reduced immunoglobulin levels compared with wild-type mice. The deletion of IgM totally abrogated development of CIA in both strains, although the anti-CII T cell response did not differ between the mMT and wild-type controls. We conclude that B cells play a crucial role in the development of CIA.

Wild waterfowl, particularly dabbling ducks such as mallards (Anas platyrhynchos), are considered the main reservoir of low-pathogenic avian influenza viruses (LPAIVs). They carry viruses that may evolve and become highly pathogenic for poultry or zoonotic. Understanding the ecology of LPAIVs in these natural hosts is therefore essential. We assessed the clinical response, viral shedding and antibody production of juvenile mallards after intra-esophageal inoculation of two LPAIV subtypes previously isolated from wild congeners. Six ducks, equipped with data loggers that continually monitored body temperature, heart rate and activity, were successively inoculated with an H7N7 LPAI isolate (day 0), the same H7N7 isolate again (day 21) and an H5N2 LPAI isolate (day 35). After the first H7N7 inoculation, the ducks remained alert with no modification of heart rate or activity. However, body temperature transiently increased in four individuals, suggesting that LPAIV strains may have minor clinical effects on their natural hosts. The excretion patterns observed after both re-inoculations differed strongly from those observed after the primary H7N7 inoculation, suggesting that not only homosubtypic but also heterosubtypic immunity exist. Our study suggests that LPAI infection has minor clinically measurable effects on mallards and that mallard ducks are able to mount immunological responses protective against heterologous infections. Because the transmission dynamics of LPAIVs in wild populations is greatly influenced by individual susceptibility and herd immunity, these findings are of high importance. Our study also shows the relevance of using telemetry to monitor disease in animals.

Transfer of collagen type II (CII)-specific monoclonal antibodies induces an acute form of arthritis (collagen type II antibody-induced arthritis, CAIA) in naïve mice. Arthritis was induced using a pair of monoclonal antibodies M2139 and CIIC1, binding to J1 and C1(I) epitopes of CII, respectively. Thereafter, lipopolysaccharide injection was used to increase the incidence and severity of the disease. This model was used to investigate the effect of genes, age, and sex as well as effector cells in the end-stage effector phase of arthritis pathogenesis. Injection of a single monoclonal antibody induced arthritis only after lipopolysaccharide stimulation. CAIA showed differences in disease penetration among the susceptible strains indicating the importance of non-major histocompatibility complex genes on the antibody effector pathway. B-cell-deficient mice were susceptible to CAIA and in some genetic backgrounds B-cell deficiency leads to enhanced arthritis. Histology of the affected paws revealed massive infiltrations of neutrophils along with bone and cartilage erosion, pannus formation, and fibrin deposition. Depletion of neutrophils significantly reduced the incidence and severity of the disease. CAIA susceptibility increased with age. Males were more susceptible than females and estrogen treatment decreased the development of arthritis. We conclude that CAIA is an acute arthritis triggered by antibody binding and neutrophils bypassing immune activation but with many characteristics in common with collagen-induced arthritis.

No abstract

No abstract