Monday, 19 December 2011

Research: B cells and Gut flora

Fritz JH et al. Acquisition of a multifunctional IgA(+) plasma cell phenotype in the gut.Nature. 2011 Dec 11. doi: 10.1038/nature10698

The largest mucosal surface in the body is in the gastrointestinal tract (the gut), a location that is heavily colonized by microbes that are normally harmless. A key mechanism required for maintaining a homeostatic balance between this microbial burden and the lymphocytes that densely populate the gastrointestinal tract is the production and transepithelial transport of poly-reactive IgA antibody.

Within the mucosal tissues, B cells respond to cytokines, sometimes in the absence of T-cell help, undergo class switch recombination of their immunoglobulin receptor to IgA, and differentiate to become plasma cells (cells that produce antibodies). However, IgA-secreting plasma cells probably have additional attributes that are needed for coping with the tremendous bacterial load in the gastrointestinal tract.

The article reports that mouse IgA(+) plasma cells also produce the anti-microbial mediators tumour-necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS), and express many molecules that are commonly associated with monocyte/granulocytic cell types. The development of iNOS-producing IgA(+) plasma cells can be recapitulated in vitro in the presence of gut stroma, and the acquisition of this multifunctional phenotype in vivo and in vitro relies on microbial co-stimulation. Deletion of TNF-α and iNOS in B-lineage cells resulted in a reduction in IgA production, altered diversification of the gut microbiota and poor clearance of a gut-tropic pathogen. These findings reveal a novel adaptation to maintaining normal balance in the gut, and extend the repertoire of protective responses exhibited by some B-lineage cells.

There has been a long-standing mystery of how certain cells can differentiate between and attack harmful bacteria in the intestine without damaging beneficial bacteria and other necessary cells. The researchers found that some B cells acquire functions that allow them to neutralize pathogens only while spending time in the gut. However, how this could link to anything to do with MS, is just a tentative media story line. Gut microflora appears to be the new "flavour of the month"so we can expect more clarity in the future


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