Portugal Silvia, Tipton Christopher M, Sohn Haewon, Kone Younoussou, Wang Jing, Li Shanping, Skinner Jeff, Virtaneva Kimmo, Sturdevant Daniel E, Porcella Stephen F, Doumbo Ogobara K, Doumbo Safiatou, Kayentao Kassoum, Ongoiba Aissata, Traore Boubacar, Sanz Inaki, Pierce Susan K, Crompton Peter D
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States.
Departments of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, United States.
Elife. 2015 May 8;4:e07218. doi: 10.7554/eLife.07218.
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.
恶性疟原虫疟疾中的保护性抗体只有在多年反复感染后才能获得。长期接触疟疾与非典型记忆B细胞（MBCs）大量增加有关，这些细胞类似于在多种持续性病毒感染中扩增的B细胞。了解非典型MBCs的功能及其与经典MBCs的关系对于开发针对疟疾和其他慢性感染的有效疫苗至关重要。我们发现，非典型和经典MBCs的VH基因库和体细胞超突变率没有区别，这表明它们有共同的发育史。非典型MBCs表达一系列抑制性受体，且非典型MBCs中的B细胞受体（BCR）信号传导受阻，导致B细胞反应受损，包括增殖、细胞因子产生和抗体分泌。因此，在长期接触疟疾的情况下，非典型MBCs似乎从经典MBCs分化而来，变得对BCR介导的激活具有抗性，并可能干扰疟疾免疫力的获得。
