Naive B cells and IL-10

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Naive B cells and IL-10

Postby TwistedHelix » Sat May 05, 2007 6:52 am

Cytokines are the molecules which cells use to communicate with each other. Some of them, like IL-10, turn down inflammation, while others turn it up. In MS the levels of these molecules are out of balance, with too little IL-10 being produced.
It seems that IL-10 is normally made by "naive" B cells, which are "blank" cells that haven't been exposed to enemy tissue, while the inflammatory cytokines are made by "memory" B cells, which are the ones which have been exposed and "remember" a previous antigen.
Therefore the distinct populations of naive cells and memory cells may play an important role in establishing this balance, and why therapies targeting B cells are in the pipeline. That's my interpretation of the abstract below, anyway:

Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis.

J Immunol. 2007 May 15;178(10):6092-9

Authors: Duddy M, Niino M, Adatia F, Hebert S, Freedman M, Atkins H, Kim HJ, Bar-Or A

Although recent animal studies have fuelled growing interest in Ab-independent functions of B cells, relatively little is known about how human B cells and their subsets may contribute to the regulation of immune responses in either health or disease. In this study, we first confirm that effector cytokine production by normal human B cells is context dependent and demonstrate that this involves the reciprocal regulation of proinflammatory and anti-inflammatory cytokines. We further report that this cytokine network is dysregulated in patients with the autoimmune disease multiple sclerosis, whose B cells exhibit a decreased average production of the down-regulatory cytokine IL-10. Treatment with the approved chemotherapeutic agent mitoxantrone reciprocally modulated B cell proinflammatory and anti-inflammatory cytokines, establishing that the B cell cytokine network can be targeted in vivo. Prospective studies of human B cells reconstituting following in vivo depletion suggested that different B cell subsets produced distinct effector cytokines. We confirmed in normal human B cell subsets that IL-10 is produced almost exclusively by naive B cells while the proinflammatory cytokines lymphotoxin and TNF-alpha are largely produced by memory B cells. These results point to an in vivo switch in the cytokine "program" of human B cells transitioning from the naive pool to the memory pool. We propose a model that ascribes distinct and proactive roles to memory and naive human B cell subsets in the regulation of memory immune responses and in autoimmunity. Our findings are of particular relevance at a time when B cell directed therapies are being applied to clinical trials of several autoimmune diseases.

PMID: 17475834 [PubMed - in process]
Dom
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Postby bromley » Sat May 05, 2007 8:12 am

Dom,

Great post.

A plus point from the recent AAN conference was the results from two early Rituxan trials (a therapy which depletes B cells). The results look promising, but perhaps more importantly they are providing some insights into the role of B cells in MS.

Ian
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Postby TwistedHelix » Mon May 07, 2007 5:01 am

Thanks Ian,

I hope you had a good holiday, and how is the redoubtable Ms Chalmers?
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