期刊
NATURE IMMUNOLOGY
卷 21, 期 7, 页码 790-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41590-020-0678-5
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资金
- NCI [P30CA086862]
- National Center for Research Resources of the NIH [S10OD016199]
- American Heart Association [16PRE27660002]
- NIH [AI125446, AI127481, AI139902, T32 AI007485, T32 GM067795, AI134733, AI121080, AI139874]
- Veteran Affairs BLR&D Merit Review Program [BX002903]
- NHMRC Senior Research Fellowship [1154265]
- NHMRC Program grant [1132975]
- NHMRC Practitioner Fellowship [1135955]
- NHMRC Career Development Fellowship [1141632]
- NHMRC Project Grant [1141278]
- Medicine for Malaria Venture
- National Health and Medical Research Council of Australia [1154265, 1135955, 1141278, 1141632, 1132975] Funding Source: NHMRC
Plasmodium parasite-specific antibodies are critical for protection against malaria, yet the development of long-lived and effective humoral immunity against Plasmodium takes many years and multiple rounds of infection and cure. Here, we report that the rapid development of short-lived plasmablasts during experimental malaria unexpectedly hindered parasite control by impeding germinal center responses. Metabolic hyperactivity of plasmablasts resulted in nutrient deprivation of the germinal center reaction, limiting the generation of memory B cell and long-lived plasma cell responses. Therapeutic administration of a single amino acid to experimentally infected mice was sufficient to overcome the metabolic constraints imposed by plasmablasts and enhanced parasite clearance and the formation of protective humoral immune memory responses. Thus, our studies not only challenge the current model describing the role and function of blood-stage Plasmodium-induced plasmablasts but they also reveal new targets and strategies to improve anti-Plasmodium humoral immunity. Early humoral responses to malaria fail to induce durable protective antibodies. Butler and colleagues report that low-affinity, short-lived plasmablasts become nutrient sinks for glutamine and starve germinal center B and T cells, thereby reducing the generation of high-affinity B cells and long-lived plasma cells and memory B cells.
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