Macropinocytosis-dependent endocytosis of Japanese flounder IgM(+) B cells and its regulation by CD22
FISH & SHELLFISH IMMUNOLOGY
Authors: Li, Yi-qun; Sun, Li; Li, Jun
Abstract
B cells in fish are proven to be endocytic and have a great contribution to innate immunity like phagocytosis. In this study, the endocytic capacity and the corresponding internalization pathways of IgM(+) B cells in Japanese flounder (Paralichthys olivaceus) were investigated. The results showed that IgM(+) B cells in peripheral blood leukocytes (PBL) and splenic leukocytes (SL) exhibited different abilities to ingest 0.5 mu m and 1 pm latex beads through macropinocytosis-dependent endocytic pathway. Japanese flounder CD22 (PoCD22) co-stimulatory signals were identified to be essential for the innate immune responses in B cells. Most of IgM+ B cells and some IgM(-) cells were demonstrated to be PoCD22 positive. When PoCD22 was blocked by antibody, the endocytic activities and reactive oxygen species (ROS) activities of SL IgM(+) B cells were significantly increased, while the endocytic and ROS activities of PBL IgM(+) B cells were significant decreased. These results collectively suggest that Japanese flounder IgM(+) B cells are able to employ macropinocytosis-dependent endocytic pathway, which is under the regulation of CD22.
Epratuzumab for the treatment of systemic lupus erythematosus
EXPERT REVIEW OF CLINICAL IMMUNOLOGY
Authors: Geh, Daniel; Gordon, Caroline
Abstract
Introduction: Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease. There are three drugs licensed for the treatment of lupus: corticosteroids, hydroxychloroquine and belimumab. Immunosuppressants such as azathioprine, methotrexate and mycophenolate are also used. Despite these treatments there is still considerable morbidity. New treatments are needed for the management of active lupus. Epratuzumab a humanized IgG1 monoclonal antibody that targets CD22 resulting in selective B cell modulation that has been considered a potential treatment for SLE.Areas covered: Summary of the relevant pathogenesis and disease activity measurements used in SLE patients, current treatments and unmet needs in SLE, pharmacokinetics and pharmacodynamics of epratuzumab therapy, and a summary of the 7 clinical trials that have investigated the efficacy and safety of epratuzumab in SLE.Expert commentary: It is not clear why trials have failed to demonstrate efficacy but high placebo response rates from optimisation of standard of care and a sub-optimal dosing regimen may have played a role. Post-hoc analysis suggested that there may be subgroups that did respond, such as anti-SSA positive patients with features of Sjogren's syndrome. Further research is needed to explore this and other potential sub-groups that might respond.