Plasmodium-specific atypical memory B cells are short-lived activated B cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA473982 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7241810_1.fastq.gz | Fastqsanger.gz | |||
| SRR7241810_2.fastq.gz | Fastqsanger.gz | |||
| SRR7241820_1.fastq.gz | Fastqsanger.gz | |||
| SRR7241820_2.fastq.gz | Fastqsanger.gz | |||
| SRR7241811_1.fastq.gz | Fastqsanger.gz |
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Project description:Chronic infections such as HIV, tuberculosis and malaria in humans are associated with the appearance of atypical memory B cells in peripheral blood. It has been suggested that these B cells do not function normally as memory cells, and thus may be responsible for poor acquisition of immunity and maintenance of chronic infections. Studies on these cells in human infections are limited by the lack of accessibility to lymphoid organs, and relevant mouse models would be valuable to investigate their development, functional capacities, and role. To investigate Plasmodium-specific memory B-cell responses during malaria, we generated an immunoglobin heavy chain knock-in mouse with a B-cell receptor that recognizes the merozoite surface protein (MSP)-1 of the rodent malaria parasite, Plasmodium chabaudi. Using this mouse and a P. chabaudi infection initiated by infected mosquito bites we show that antigen-specific B cells with many characteristics of human atypical memory B cells are generated. These cells are immunoglobulin class-switched and express, among others, the cell surface molecules CD11c, CD11b, FCRL5, and some inhibitory receptors including PD1 and LAIR-1, as well as the transcription factor T-bet. Antigen-specific atypical memory B cells are detected side-by-side with classical memory B cells during chronic blood-stage infection. Whereas classical memory B cells persist after complete infection clearance, atypical memory B cells are short-lived and disappear from the spleen at the resolution of chronic infection. Short-lived Plasmodium-specific atypical B cells also appear transiently after immunization with a TLR7/8 ligand and MSP-1. Our data suggest that these atypical memory B cells are not a subset of memory B cells, but rather antigen-experienced activated cells, and part of a normal ongoing response. Their persistence over weeks in malaria and other infections may be a consequence of continued and chronic antigenic stimulation.
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Project description:A subset of atypical memory B cells accumulates in malaria and several infections, autoimmune disorders and aging in both humans and mice. It has been suggested these cells are exhausted long-lived memory B cells, and their accumulation may contribute to poor acquisition of long-lasting immunity to certain chronic infections, such as malaria and HIV. Here, we generated an immunoglobulin heavy chain knock-in mouse with a BCR that recognizes MSP1 of the rodent malaria parasite, Plasmodium chabaudi. In combination with a mosquito-initiated P. chabaudi infection, we show that Plasmodium-specific atypical memory B cells are short-lived and disappear upon natural resolution of chronic infection. These cells show features of activation, proliferation, DNA replication, and plasmablasts. Our data demonstrate that Plasmodium-specific atypical memory B cells are not a subset of long-lived memory B cells, but rather short-lived activated cells, and part of a physiologic ongoing B-cell response.
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