Publication Date:
2013-10-22
Description:
Influenza A virus-specific B lymphocytes and the antibodies they produce protect against infection. However, the outcome of interactions between an influenza haemagglutinin-specific B cell via its receptor (BCR) and virus is unclear. Through somatic cell nuclear transfer we generated mice that harbour B cells with a BCR specific for the haemagglutinin of influenza A/WSN/33 virus (FluBI mice). Their B cells secrete an immunoglobulin gamma 2b that neutralizes infectious virus. Whereas B cells from FluBI and control mice bind equivalent amounts of virus through interaction of haemagglutinin with surface-disposed sialic acids, the A/WSN/33 virus infects only the haemagglutinin-specific B cells. Mere binding of virus is not sufficient for infection of B cells: this requires interactions of the BCR with haemagglutinin, causing both disruption of antibody secretion and FluBI B-cell death within 18 h. In mice infected with A/WSN/33, lung-resident FluBI B cells are infected by the virus, thus delaying the onset of protective antibody release into the lungs, whereas FluBI cells in the draining lymph node are not infected and proliferate. We propose that influenza targets and kills influenza-specific B cells in the lung, thus allowing the virus to gain purchase before the initiation of an effective adaptive response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863936/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863936/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dougan, Stephanie K -- Ashour, Joseph -- Karssemeijer, Roos A -- Popp, Maximilian W -- Avalos, Ana M -- Barisa, Marta -- Altenburg, Arwen F -- Ingram, Jessica R -- Cragnolini, Juan Jose -- Guo, Chunguang -- Alt, Frederick W -- Jaenisch, Rudolf -- Ploegh, Hidde L -- DP1 GM106409/GM/NIGMS NIH HHS/ -- R01 AI033456/AI/NIAID NIH HHS/ -- R01 AI087879/AI/NIAID NIH HHS/ -- R01 GM100518/GM/NIGMS NIH HHS/ -- R01 HD045022/HD/NICHD NIH HHS/ -- R37 HD045022/HD/NICHD NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Nov 21;503(7476):406-9. doi: 10.1038/nature12637. Epub 2013 Oct 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24141948" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antibodies/immunology/metabolism
;
Antibody Specificity/immunology
;
B-Lymphocytes/*immunology/pathology/secretion/*virology
;
Cell Death
;
Female
;
Hemagglutinin Glycoproteins, Influenza Virus/immunology/metabolism
;
Immunoglobulin G/immunology/metabolism
;
Lung/cytology/immunology/secretion/virology
;
Lymph Nodes/cytology/immunology
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Molecular Sequence Data
;
Neutralization Tests
;
Nuclear Transfer Techniques
;
Orthomyxoviridae/pathogenicity/*physiology
;
Receptors, Antigen, B-Cell/*immunology/metabolism
;
Virus Replication
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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