Antibody Effector Functions Mediated by FcY-Receptors Are Compromised during Persistent Viral Infection

Summary T cell dysfunction is well documented during chronic viral infections but little is known about functional abnormalities in humoral immunity. Here we report that mice persistently infected with lymphocytic choriomeningitis virus (LCMV) exhibit a severe defect in Fcγ-receptor (FcγR)-mediated antibody effector functions. Using transgenic mice expressing human CD20, we found that chronic LCMV infection impaired the depletion of B cells with rituximab, an anti-CD20 antibody widely used for the treatment of B cell lymphomas. In addition, FcγR-dependent activation of dendritic cells by agonistic anti-CD40 antibody was compromised in chronically infected mice. These defects were due to viral antigen-antibody complexes and not the chronic infection per se, because FcγR-mediated effector functions were normal in persistently infected mice that lacked LCMV-specific antibodies. Our findings have implications for the therapeutic use of antibodies and suggest that high levels of pre-existing immune complexes could limit the effectiveness of antibody therapy in humans

Antibody Effector Functions Mediated by FcY-Receptors Are Compromised during Persistent Viral Infection

Summary T cell dysfunction is well documented during chronic viral infections but little is known about functional abnormalities in humoral immunity. Here we report that mice persistently infected with lymphocytic choriomeningitis virus (LCMV) exhibit a severe defect in Fcγ-receptor (FcγR)-mediated antibody effector functions. Using transgenic mice expressing human CD20, we found that chronic LCMV infection impaired the depletion of B cells with rituximab, an anti-CD20 antibody widely used for the treatment of B cell lymphomas. In addition, FcγR-dependent activation of dendritic cells by agonistic anti-CD40 antibody was compromised in chronically infected mice. These defects were due to viral antigen-antibody complexes and not the chronic infection per se, because FcγR-mediated effector functions were normal in persistently infected mice that lacked LCMV-specific antibodies. Our findings have implications for the therapeutic use of antibodies and suggest that high levels of pre-existing immune complexes could limit the effectiveness of antibody therapy in humans

The Perfective, the Progressive and the (dis)closure of situations: comment on the paper by María J. Arche

In the present paper, inspired by María J. Arche’s work, “The construction of viewpoint aspect: the imperfective revisited” (2013, this issue), I add several pieces of evidence in favor of her proposal that viewpoint aspect does not alter the fundamental situation aspect properties of predicates. Namely, I discuss the temporal interpretations in Capeverdean, a Portuguese-based Creole language for which the salient opposition in the domain of viewpoint aspect is not between the imperfective and the perfective, but rather between the Progressive and the Perfect, here taken as semantically complex categories that involve certain temporal characteristics; crucially, imperfectivity is one of the features of the Progressive and a perfective viewpoint is part of the semantic complexity of the Perfect. I also discuss the role of for-time durational adverbials when combined with the perfective and propose that, in their presence, the relevant final boundary when telic predicates are at stake is not the culmination of the event, but rather the final point described by that time-argument. This proposal accounts nicely for the fact that, in these specific contexts, there is no contradiction in having this perfective clause conjoined with the assertion that the underlying telic situation is not completed.info:eu-repo/semantics/publishedVersio