Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function
Silvia Portugal, Christopher M Tipton, Haewon Sohn, Younoussou Kone, Jing Wang, Shanping Li, Jeff Skinner, Kimmo Virtaneva, Daniel E Sturdevant, Stephen F Porcella, Ogobara K Doumbo, Safiatou Doumbo, Kassoum Kayentao, Aissata Ongoiba, Boubacar Traore, Inaki Sanz, Susan K Pierce, Peter D Crompton, Silvia Portugal, Christopher M Tipton, Haewon Sohn, Younoussou Kone, Jing Wang, Shanping Li, Jeff Skinner, Kimmo Virtaneva, Daniel E Sturdevant, Stephen F Porcella, Ogobara K Doumbo, Safiatou Doumbo, Kassoum Kayentao, Aissata Ongoiba, Boubacar Traore, Inaki Sanz, Susan K Pierce, Peter D Crompton
Abstract
Protective antibodies in Plasmodium falciparum malaria are only acquired after years of repeated infections. Chronic malaria exposure is associated with a large increase in atypical memory B cells (MBCs) that resemble B cells expanded in a variety of persistent viral infections. Understanding the function of atypical MBCs and their relationship to classical MBCs will be critical to developing effective vaccines for malaria and other chronic infections. We show that VH gene repertoires and somatic hypermutation rates of atypical and classical MBCs are indistinguishable indicating a common developmental history. Atypical MBCs express an array of inhibitory receptors and B cell receptor (BCR) signaling is stunted in atypical MBCs resulting in impaired B cell responses including proliferation, cytokine production and antibody secretion. Thus, in response to chronic malaria exposure, atypical MBCs appear to differentiate from classical MBCs becoming refractory to BCR-mediated activation and potentially interfering with the acquisition of malaria immunity.
Keywords: Plasmodium falciparum; atypical memory B cells; human; immunology; infectious disease; malaria; microbiology.
Conflict of interest statement
The authors declare that no competing interests exist.
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References
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