B-1 B Cells As A Source Of Polyreactive IgE Antibodies, In Allergic Individuals
Funder
National Health and Medical Research Council
Funding Amount
$331,320.00
Summary
Allergic disease results from the actions of antibody molecules that are produced by cells called B cells. Over the last fifteen years, it has been realised that there are at least two B cell subsets, called B-1 and B-2 cells. The B-1 cells and their antibody products have many unusual features, and they have been implicated in some disease processes. We have recently completed studies that strongly suggest that B-1 B cells may play an important role in some allergic disease. We wish to compare ....Allergic disease results from the actions of antibody molecules that are produced by cells called B cells. Over the last fifteen years, it has been realised that there are at least two B cell subsets, called B-1 and B-2 cells. The B-1 cells and their antibody products have many unusual features, and they have been implicated in some disease processes. We have recently completed studies that strongly suggest that B-1 B cells may play an important role in some allergic disease. We wish to compare groups of patients defined according to their allergic conditions and age, to see whether B-1 B cell activity is associated with particular allergic diseases. We hypothesise that patients with allergic skin conditions have raised numbers of allergy-inducing B-1 cells. Such patients will be compared with those with allergies to inhalent allergens and others with food allergies. Studies will be performed in adult groups as well as in children, for B-1 B cell numbers are known to vary with age. As most of our understanding of the regulation of B cell function, in the context of allergic disease, has arisen from studies conducted with conventional B-2 cells, we also wish to reconsider aspects of B cell regulation. We are specifically interested in the regulation of the 'switching' of B-1 B cells, when they change from the production of antibodies of a 'non-allergic' type (IgM antibodies) to allergy-promoting IgE antibodies. We wish to determine whether the B-1 B cells of allergic individuals are particularly susceptible to such switching, when under the influence of regulatory molecules called cytokines. We expect that B-1 B cells will be associated with some, though not all allergic conditions, and that these cells will emerge as a new target for therapies. Such a finding would be most important. The development of new therapies will require a better understanding of the regulation of these cells, and this will be another important outcome of this project.Read moreRead less
Role Of Maternal Dietary Omega3 Fatty Acids In Modulation Of Allergen-specific T Cell Responses In The Offspring
Funder
National Health and Medical Research Council
Funding Amount
$287,036.00
Summary
Environmental lifestyle changes are implicated in the concerning increase in allergic diseases such as asthma and allergic diseases over the 25 years. Despite the enormous personal, social and economic cost, the exact causes are not clear. Diet is one of the most important yet unstudied environmental exposures linked to the recent increase in both asthma and allergic disease. Authorities in this area have recommended diet as research priority in the search for allergy prevention strategies. Alle ....Environmental lifestyle changes are implicated in the concerning increase in allergic diseases such as asthma and allergic diseases over the 25 years. Despite the enormous personal, social and economic cost, the exact causes are not clear. Diet is one of the most important yet unstudied environmental exposures linked to the recent increase in both asthma and allergic disease. Authorities in this area have recommended diet as research priority in the search for allergy prevention strategies. Allergic diseases result from inappropriate inflammatory immune responses to protein substances such as dust mite (allergens), and it now evident that these patterns of immune responses are commonly initiated before birth. This study will address the influence of maternal diet in pregnancy on the developing human immune system, and how it contributes to the development of allergic immune responses in offspring. One of the most significant dietary changes associated with increasing urbanisation is the increasing intake of pro-inflammatory omega-6 fatty acids (which may promote allergic immune responses) and declining dietary levels of omega-3 fatty acids (which inhibit inflammatory immune responses). Omega-3 fatty acids have beneficial effects in many inflammatory diseases, and are important for healthy pregnancy. It is possible that maternal diets which are becoming increasingly deficient in omega-3 fatty acids may prime the fetus to respond more readily to allergens, and increase the risk of later allergic responses. This study will determine whether increasing dietary omega-3 fatty acids during pregnancy using fish oil supplements, can alter immune responses to house dust mite and other allergens at birth and later infancy. The findings will contribute to our understanding of the relationship between antenatal nutrition and immune development and may lead to dietary recommendations as a cost effective, non invasive strategy to help prevent allergic disease.Read moreRead less