Abstract
In order to better understand how the immune system interacts with environmental triggers to produce organ-specific disease, we here address the hypothesis that B and plasma cells are free to migrate through the mucosal surfaces of the upper and lower respiratory tracts, and that their total antibody repertoire is modified in a common respiratory tract disease, in this case atopic asthma. Using Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) we have catalogued the antibody repertoires of B cell clones retrieved near contemporaneously from multiple sites in the upper and lower respiratory tract mucosa of adult volunteers with atopic asthma and non-atopic controls and traced their migration. We show that the lower and upper respiratory tracts are immunologically connected, with trafficking of B cells directionally biased from the upper to the lower respiratory tract and points of selection when migrating from the nasal mucosa and into the bronchial mucosa. The repertoires are characterized by both IgD-only B cells and others undergoing class switch recombination, with restriction of the antibody repertoire distinct in asthmatics compared with controls. We conclude that B cells and plasma cells migrate freely throughout the respiratory tract and exhibit distinct antibody repertoires in health and disease.
Highlights
The respiratory tract is located inside the body but, like the digestive and reproductive tracts, is constantly exposed to the external environment with its plethora of stimuli from microorganisms, proteins including allergens and other particulate matter including particulate pollution
All other directional comparisons only showed a significantly greater proportion of trafficking events in a maximum of two individuals suggesting no general importance. These results indicate that a biased ancestor/descendant relationship from the nasal to the bronchial mucosa is the dominant pattern in the analyzed trees, providing further evidence that, in asthmatics, the immune response can be initiated in the nose and that activated B cells can traffic to the bronchial tissue, accumulating mutations either within the bronchial mucosa or at unknown sites en route from the nasal to the bronchial mucosa
We found that the CDR3 length was significantly increased in both nasal and bronchial global sequences of IgA and IgG isotype (p
Summary
The respiratory tract is located inside the body but, like the digestive and reproductive tracts, is constantly exposed to the external environment with its plethora of stimuli from microorganisms, proteins including allergens and other particulate matter including particulate pollution. The respiratory tract is divided into upper and lower regions above and below the larynx, the former comprising the nasal cavity, paranasal sinuses and pharynx and the latter the trachea and bronchial tree. It is contiguous with the skin (via the nostrils) and the conjunctiva (via the nasolacrimal ducts). Lymphoid tissue surrounds the upper respiratory tract (Waldeyer’s Ring, which includes the lingual tonsils and the adenoids), while lymph nodes are abundant adjacent to the lower airways in the mediastinum and adjacent to the trachea and bronchi. Lymph flows towards the hilum and returns to the systemic venous circulation via the right lymphatic and left thoracic ducts
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