Nature: Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus

[tetano]

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Nature | Letter




Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus

Stephanie K. Dougan1, 4
Joseph Ashour1, 4
Roos A. Karssemeijer1
Maximilian W. Popp1, 2
Ana M. Avalos1
Marta Barisa1
Arwen F. Altenburg1
Jessica R. Ingram1
Juan Jose Cragnolini1
Chunguang Guo3
Frederick W. Alt3
Rudolf Jaenisch1
Hidde L. Ploegh1, 2

Affiliations
Contributions
Corresponding author

Nature
(2013)
doi:10.1038/nature12637

Received
24 May 2013
Accepted
04 September 2013
Published online
20 October 2013


Influenza A virus-specific B lymphocytes and the antibodies they produce protect against infection1. 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.

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12637.html

 

[gsgs]

Re: Nature: Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus

but this is accidental and not targeted flu-evolution (?)


successful flu needn't replicate in the lungs

and flu evolution doesn't care about humans,
they are specialized on mallards

 

[JJackson]

Re: Nature: Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus

but this is accidental and not targeted flu-evolution (?)


successful flu needn't replicate in the lungs

and flu evolution doesn't care about humans,
they are specialized on mallards

gs Am I missing something here?
All evolution is accidental and the useful is selected for. This definately seems to be useful - to the virus - as it targets the hosts immune defences reducing the effectiveness of the targeted B-cells in the lung.

Flu does not need the lungs but the lungs are its easiest way in for mammalian flus. They are easy to get to, for an air born pathogen, and one of the few places with the right combination of binding sites and proteases.

The flu here does care about humans because it has jumped the species barrier and is no-longer an avian flu but a human optimised one. Both PR/8 and WSN/33 are human flus and probably would not fare well in a mallard.

I do not have full access but was curious as to why the the B-cells in the draining lymph nodes were not attacked but those in the lung were. Anyone know of the significant difference?

 

[gsgs]

Re: Nature: Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus

what flu-A learns in humans will be lost when the strain dies and is replaced in the next pandemic with a new avian one

humans are a dead end for flu-A evolution