TY - JOUR TI - Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function AU - Portugal, Silvia AU - Tipton, Christopher M AU - Sohn, Haewon AU - Kone, Younoussou AU - Wang, Jing AU - Li, Shanping AU - Skinner, Jeff AU - Virtaneva, Kimmo AU - Sturdevant, Daniel E AU - Porcella, Stephen F AU - Doumbo, Ogobara K AU - Doumbo, Safiatou AU - Kayentao, Kassoum AU - Ongoiba, Aissata AU - Traore, Boubacar AU - Sanz, Inaki AU - Pierce, Susan K AU - Crompton, Peter D A2 - Krzych, Urszula VL - 4 PY - 2015 DA - 2015/05/08 SP - e07218 C1 - eLife 2015;4:e07218 DO - 10.7554/eLife.07218 UR - https://doi.org/10.7554/eLife.07218 AB - 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. KW - atypical memory B cell KW - Plasmodium falciparum KW - malaria JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -