The Regulation of Inherently Autoreactive VH4-34–Expressing B Cells in Individuals Living in a Malaria-Endemic Area of West Africa

Abstract

Plasmodium falciparum malaria is a deadly infectious disease in which antibodies play a critical role in naturally acquired immunity. However, at present the specificity and nature of antibodies elicited in response to malaria is only partially understood. Autoreactivity and polyreactivity are common features of antibody responses in several infections and have been suggested to contribute to effective pathogen-specific antibody responses. Here we report on the regulation of B cells expressing the inherently autoreactive VH4-34 heavy chain (identified by the 9G4 monoclonal antibody) and 9G4+ plasma IgG in adults and children living in a P. falciparum malaria-endemic area in West Africa. The frequency of 9G4+ peripheral blood CD19+ B cells was similar in U.S. adults and African adults and children. However, more 9G4+ B cells appeared in classical and atypical memory B cell compartments in African children and adults as compared to U.S. adults. The levels of 9G4+ IgG increased following acute febrile malaria, but did not increase with age as humoral immunity is acquired or correlate with protection from acute disease. This was the case even though a portion of 9G4+ B cells acquired phenotypes of atypical and classical memory B cells and 9G4+ IgG contained equivalent numbers of somatic hypermutations as compared to all other VHs, a characteristic of secondary antibody repertoire diversification in response to antigen stimulation. Determining the origin and function of 9G4+ B cells and 9G4+ IgG in malaria may contribute to a better understanding of the varied roles of autoreactivity in infectious diseases.

BAFF inhibition in SLE—Is tolerance restored?

“…VH4-34 heavy chain family are expanded in the memory compartment of malaria patients, 72 suggesting a link between relaxed B cell developmental selection and robust pathogen responses.…”

Why blood group A individuals are at risk whereas blood group O individuals are protected from SARS-CoV-2 (COVID-19) infection: A hypothesis regarding how the virus invades the human body via ABO(H) blood group-determining carbohydrates

“…It is assumed that during SARS-CoV-2 infection, especially in the non-O blood groups, the induction of autoimmune processes might contribute to the development of severe symptoms, which may even be dominated by autoimmune inflammation. In fact, this phenomenon has been observed in severe cases of malaria tropica ( Hart et al, 2016 , Rivera-Correa et al, 2017 ). It has been explained by the author through hybridization ( Arend, 2020b ), but awaits elucidation through studies of the complex mechanisms of cellular immunity, which is ignored in this manuscript that exclusively is focused on the ABO(H) blood group phenotype-determined humoral innate immunity and the first steps of pathogenesis.…”

Why Blood Group A Individuals Are at Risk Whereas Blood Group O Individuals Might Be Protected from SARS-CoV-2 (COVID-19) Infection: A Hypothesis Regarding How the Virus Invades the Human Body via Abo(H) Blood Group-Determining Carbohydrates

“…2: blood group O(H), which is bound to the virus solely by the formation of the hybrid H-type antigen, has the least contact with the pathogen and is the most protected group when it loses only the anti-H isoagglutinin, but retains the innate anti-A and anti-B isoagglutinin reactivities, involving secondary It is assumed that during SARS-CoV-2 infection, especially in the non-O blood groups, the induction of autoimmune processes might contribute to the development of severe symptoms, which may even be dominated by autoimmune inflammation. In fact, this phenomenon has been observed in severe cases of malaria tropica (Hart et al, 2016;Rivera-Correa et al, 2017). It has been explained by the author through hybridization (Arend, 2020b) In blood group A, the anti-A and anti-H formations are physiologically blocked, a decrease in the level of anti-B isoagglutinin is observed, and neither anti-A-nor anti-B-reactive IgG is produced.…”