Incomplete genetic reconstitution of B cell pools contributes to prolonged immunosuppression after measles

Abstract

Measles is a disease caused by the highly infectious measles virus (MeV) that results in both viremia and lymphopenia. Lymphocyte counts recover shortly after the disappearance of measles-associated rash, but immunosuppression can persist for months to years after infection, resulting in increased incidence of secondary infections. Animal models and in vitro studies have proposed various immunological factors underlying this prolonged immune impairment, but the precise mechanisms operating in humans are unknown. Using B cell receptor (BCR) sequencing of human peripheral blood lymphocytes before and after MeV infection, we identified two immunological consequences from measles underlying immunosuppression: (i) incomplete reconstitution of the naïve B cell pool leading to immunological immaturity and (ii) compromised immune memory to previously encountered pathogens due to depletion of previously expanded B memory clones. Using a surrogate model of measles in ferrets, we investigated the clinical consequences of morbillivirus infection and demonstrated a depletion of vaccine-acquired immunity to influenza virus, leading to a compromised immune recall response and increased disease severity after secondary influenza virus challenge. Our results show that MeV infection causes changes in naïve and memory B lymphocyte diversity that persist after the resolution of clinical disease and thus contribute to compromised immunity to previous infections or vaccinations. This work highlights the importance of MeV vaccination not only for the control of measles but also for the maintenance of herd immunity to other pathogens, which can be compromised after MeV infection.

Vertically Transferred Immunity in Neonates: Mothers, Mechanisms and Mediators

“…Resulting from the global rise of vaccine hesitancy, one of the 10 threats to global health (52), transmission of measles is rapidly spreading, which poses a significant hazard to children's health. Besides common complications related to measles infection in children, such as diarrhea, middle ear infection and pneumonia (53), it has recently been identified that measles can obliterate existing humoral immune memory against a repertoire of pathogens (54,55). The incomplete reconstitution of the naïve B cell pool and the depletion of previously expanded B memory clones account for this obliteration of immune memory (54).…”

Humoral Immunity vs. Salmonella

“…Other pathogens may also have an ability to suppress humoral immunity. Recent studies indicated that respiratory syncytial virus (RSV) infection fails to induce in IgA + memory B cells (50) and that measles causes elimination of 11-73% of the antibody repertoire and depletion of previously expanded B memory clones after infection (51,52). However, cellular and molecular mechanisms on their suppression are still unknown and should be investigated, then comparing with the case of Salmonella.…”

Measles: An Overview of a Re-Emerging Disease in Children and Immunocompromised Patients

“…Nonetheless, very recently, Petrova et al [68] identified the long-term consequences of MV infection: Incomplete reconstitution of the naive B cell pool and a compromised immune memory to previously encountered pathogens. Similar results have also been shown by Mina et al [69].…”