Monoclonal IgM rheumatoid factor-like anti-globulins enhance the inhibitory effects ofPlasmodium falciparum-specific monoclonal antibodiesin vitro

Abstract

Monoclonal IgM rheumatoid factor-like anti-globulins were produced by in vitro stimulation of naive BALB/c spleen cells with lipopolysaccharide, and by hyperimmunization of mice with merozoites of Plasmodium falciparum, followed by fusion of the spleen cells to mouse myelomas. In vitro, these anti-globulins augmented the inhibitory effects of P. falciparum-specific polyclonal mouse sera and monoclonal IgG1 and IgG2b antibodies by binding to Fc fragments of IgG molecules attached to blood-stage parasites. In some instances, the presence of anti-globulins correlated with an increase in the number of schizonts which failed to disperse merozoites. In other cases, parasitaemia remained low in the absence of the schizont inhibition phenomenon, suggesting that anti-globulins contribute to host cell protection not only by agglutinating merozoites, but also by increasing the density of the antibody coat surrounding the parasites, thus interfering with parasite receptor-erythrocyte ligand interactions. The anti-globulins were not inhibitory when added to parasite cultures containing IgG not specific for P. falciparum. These results may help explain the function of IgM anti-globulins found at elevated serum levels in some patients with malaria or other chronic infectious diseases.

Asymptomatic Plasmodium falciparum infection in children is associated with increased auto-antibody production, high IL-10 plasma levels and antibodies to merozoite surface protein 3

“…Antigens expressed by merozoites during blood-stage infection could be targets of these protective antibodies. Indeed, the IgG1 and IgG3 sub-classes have been shown to play a role in anti-merozoite responses [ 23 , 24 ]. Children in areas of high P. falciparum transmission are known to develop a strong antibody response to PfEMP1 [ 25 , 26 ].…”

“…Auto-antibodies associated with AM might be derived from CD27 + marginal zone B cells that are expanded in some auto-immune diseases. Alternatively, some of these auto-antibodies could be ‘natural antibodies’ that are produced in the absence of exogenous antigenic stimulation and that are characterized by low affinity for the antigen and polyreactivity [ 8 , 10 , 23 ]. Auto-antibodies may participate in protective mechanisms by favouring parasite clearance, which could explain the association of a high self-reactive response and with low parasitaemia (<1%) observed in AM [ 21 - 24 ].…”

Functional Memory B Cells and Long-Lived Plasma Cells Are Generated after a Single Plasmodium chabaudi Infection in Mice

“…Furthermore, the memory MSP1 19 response is composed mainly of IgG isotypes, while the primary response is initially predominated by IgM ASC. Although IgM may augment antimalarial immunity [72],[73], Abs of the IgG isotype are considered to be more superior and better suited for humoral memory than those of IgM, mainly due their longer half-lives, and more specialized effector functions. Consequently, IgG Abs allow for the maintenance of plasma Ab titres by fewer ASC than IgM Abs.…”

Rheumatoid Factors in Health and Disease: Structure, Function, Induction and Regulation

“…Moreover, the cytotoxicity of antiviral Ab is improved by RF [76]. The presence of RF can also enhance the elimination of some parasites [59,77]. RFs may potentiate the presentation of Ag to T cells in two ways: (1) the presentation of exogenous Ag may be enhanced by the uptake of ICs by dendritic cells and (2) RF B cells may themselves be particularly [78,79].…”