The latest Paper of the Month for Parasitology is “IgM+ memory B cells induced in response to Plasmodium berghei adopt a germinal centre B cell phenotype during secondary infection“

Malaria remains one the most serious infectious diseases of humans with ~200 million clinical cases every year.  The infection is transmitted to humans by the bite of Anopheles mosquitoes that are infected with parasites of the genus Plasmodium. Most cases of severe disease are caused by Plasmodium falciparum, which is endemic throughout the tropics. After a short period of replication in the liver, Plasmodium parasites find their way to the bloodstream, where they invade red blood cells, thereby avoiding recognition by the host’s immune system. These parasites in the blood are responsible for the clinical symptoms of malaria, which range from a mild febrile illness to severe complications including acute respiratory distress, renal failure, anaemia, loss of consciousness and coma.

Unlike many viral and bacterial pathogens such as smallpox and tetanus, which can induce life-long protection following a single exposure, the acquisition of immunity to the Plasmodium parasite is strikingly less efficient. Individuals living in malaria endemic areas develop immunity to clinical symptoms only after many years of repeated infections. Antibodies, made by specialised cells from the immune system called “B cells”, are a key component of this response to protect the host from subsequent infections.

During early stages of infection, some B cells make a rapid wave of “low-quality” antibodies called IgM, which are important to stop the rapid spread of infection. Later, B cells within lymph nodes and the spleen localise in structures called germinal centres. In germinal centres, B cells divide giving rise to many daughter cells and mutate their antibody genes to produce “professional B cells” able to manufacture IgG antibodies of high affinity to fight infection. Furthermore, these cells, called memory B cells, have the capacity to “remember” their cognate antigen and become activated to produce high affinity antibodies in the event of a re-infection.

Our team focuses on identifying mechanisms underlying the acquisition of immunity to malaria. Using a pre-clinical infection model, in this study we found that malaria not only induces traditional high affinity memory B cells but also “low affinity” IgM memory B cells. Our main findings revealed that during a second encounter with the malaria parasite, instead of producing antibodies, low affinity IgM memory B cells transform and rapidly acquire features that allow them return to germinal centres in lymphoid organs. Our research supports a model by which IgM memory B cells induced during malaria, might have the ability to remodel and fine-tune their affinity for antigen by accessing germinal centres upon re-infection. This response would give IgM memory B cells a good level of plasticity, which is a highly desirable feature to recognise different variants of the original parasite. Moving forward, understanding further the functional capacity of IgM memory B cells in the immune response to Plasmodium may be highly-informative to develop unanticipated tools to improve the efficacy of emerging anti-malaria vaccines.

The article “IgM+ memory B cells induced in response to Plasmodium berghei adopt a germinal centre B cell phenotype during secondary infection” by Halina M. Pietrzak, Lisa J. Ioannidis and Diana S. Hansen,  published in Parasitology,  is available free for a month.