Dataset Information

Generation of plasma cells and CD27^-IgD^- B cells during hantavirus infection is associated with distinct pathological findings.

ABSTRACT:

Objective

Human hantavirus infections can cause haemorrhagic fever with renal syndrome (HFRS). The pathogenic mechanisms are not fully understood, nor if they affect the humoral immune system. The objective of this study was to investigate humoral immune responses to hantavirus infection and to correlate them to the typical features of HFRS: thrombocytopenia and transient kidney dysfunction.

Methods

We performed a comprehensive characterisation of longitudinal antiviral B-cell responses of 26 hantavirus patients and combined this with paired clinical data. In addition, we measured extracellular adenosine triphosphate (ATP) and its breakdown products in circulation and performed in vitro stimulations to address its effect on B cells.

Results

We found that thrombocytopenia was correlated to an elevated frequency of plasmablasts in circulation. In contrast, kidney dysfunction was indicative of an accumulation of CD27^-IgD^- B cells and CD27^-/low plasmablasts. Finally, we provide evidence that high levels of extracellular ATP and matrix metalloproteinase 8 can contribute to shedding of CD27 during human hantavirus infection.

Conclusion

Our findings demonstrate that thrombocytopenia and kidney dysfunction associate with distinctly different effects on the humoral immune system. Moreover, hantavirus-infected individuals have significantly elevated levels of extracellular ATP in circulation.

SUBMITTER: Kerkman PF

PROVIDER: S-EPMC8275445 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Generation of plasma cells and CD27<sup>-</sup>IgD<sup>-</sup> B cells during hantavirus infection is associated with distinct pathological findings.

Kerkman Priscilla F PF Dernstedt Andy A Tadala Lalitha L Mittler Eva E Dannborg Mirjam M Sundling Christopher C Maleki Kimia T KT Tauriainen Johanna J Tuiskunen-Bäck Anne A Wigren Byström Julia J Ocaya Pauline P Thunberg Therese T Jangra Rohit K RK Román-Sosa Gleyder G Guardado-Calvo Pablo P Rey Felix A FA Klingström Jonas J Chandran Kartik K Puhar Andrea A Ahlm Clas C Forsell Mattias Ne MN

Clinical & translational immunology 20210712 7

<h4>Objective</h4>Human hantavirus infections can cause haemorrhagic fever with renal syndrome (HFRS). The pathogenic mechanisms are not fully understood, nor if they affect the humoral immune system. The objective of this study was to investigate humoral immune responses to hantavirus infection and to correlate them to the typical features of HFRS: thrombocytopenia and transient kidney dysfunction.<h4>Methods</h4>We performed a comprehensive characterisation of longitudinal antiviral B-cell res ...[more]

PMID: 34277007

Similar Datasets

Project description:The origin and function of blood IgM+IgD+CD27+ B cells is controversial, and they are considered a heterogeneous population. Previous staining of circulating B cells of healthy donors with rotavirus fluorescent virus-like particles allowed us to differentiate two subsets of IgM+IgD+CD27+: IgMhi and IgMlo B cells. Here, we confirmed this finding and compared the phenotype, transcriptome, in vitro function, and Ig gene repertoire of these two subsets. Eleven markers phenotypically discriminated both subsets (CD1c, CD69, IL21R, CD27, MTG, CD45RB, CD5, CD184, CD23, BAFFR, and CD38) with the IgMhi phenotypically resembling previously reported marginal zone B cells and the IgMlo resembling both naïve and memory B cells. Transcriptomic analysis showed that both subpopulations clustered close to germinal center-experienced IgM only B cells with a Principal Component Analysis, but differed in expression of 78 genes. Moreover, IgMhi B cells expressed genes characteristic of previously reported marginal zone B cells. After stimulation with CpG and cytokines, significantly (p < 0.05) higher frequencies (62.5%) of IgMhi B cells proliferated, compared with IgMlo B cells (35.37%), and differentiated to antibody secreting cells (14.22% for IgMhi and 7.19% for IgMlo). IgMhi B cells had significantly (p < 0.0007) higher frequencies of mutations in IGHV and IGKV regions, IgMlo B cells had higher usage of IGHJ6 genes (p < 0.0001), and both subsets differed in their HCDR3 properties. IgMhi B cells shared most of their shared IGH clonotypes with IgM only memory B cells, and IgMlo B cells with IgMhi B cells. These results support the notion that differential expression of IgM and IgD discriminates two subpopulations of human circulating IgM+IgD+CD27+ B cells, with the IgMhi B cells having similarities with previously described marginal zone B cells that passed through germinal centers, and the IgMlo B cells being the least differentiated amongst the IgM+CD27+ subsets.

Dataset Information

Generation of plasma cells and CD27^-IgD^- B cells during hantavirus infection is associated with distinct pathological findings.

Objective

Methods

Results

Conclusion

Publications

Generation of plasma cells and CD27<sup>-</sup>IgD<sup>-</sup> B cells during hantavirus infection is associated with distinct pathological findings.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Generation of plasma cells and CD27-IgD- B cells during hantavirus infection is associated with distinct pathological findings.

Objective

Methods

Results

Conclusion

Publications

Generation of plasma cells and CD27<sup>-</sup>IgD<sup>-</sup> B cells during hantavirus infection is associated with distinct pathological findings.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Generation of plasma cells and CD27^-IgD^- B cells during hantavirus infection is associated with distinct pathological findings.