B cells have key role in Th-mediated allergic response
medwireNews: Results of a study conducted in mouse models of allergy suggest that B cells have an important role in propagating T-helper cell (Th)-mediated responses to house dust mites (HDM).
These findings are based on experiments in which HDM-sensitized BALB/c mice were treated with an anti-CD20 antibody to deplete B cells in the lungs, or an isotype control, prior to HDM challenge on days 11, 12, and 13.
Treatment with the anti-CD20 antibody “dramatically reduced” absolute B cell numbers in the lungs of the mice, and B-cell depletion gave rise to a “pronounced effect” on the HDM-induced allergic response, report the researchers.
There were significantly lower counts of CD4+ CD44+ T cells, eosinophils, and neutrophils following HDM challenge in the lungs of B-cell-depleted mice versus those treated with the isotype control, with counts of approximately 100x10x10-3 versus 140x10x10-3 (p<0.05), 300x10x10-3 versus 550x10x10-3 (p<0.05), and 350x10x10-3 versus 550x10x10-3 (p<0.05), respectively.
These findings “reflected reduced allergic inflammation in the tissue” with B-cell depletion, and highlight “the role of B cells in amplification of Th2 responses,” say Federica Sallusto (Università della Svizzera Italiana, Bellinzona, Switzerland) and study co-authors. They note that similar reductions in T-cell, eosinophil, and neutrophil numbers were observed when the experiments were repeated using the less allergy-prone C57BL/6 strain of mouse.
Sallusto and colleagues then used fluorescently-labeled HDM (HDM-AF647) to demonstrate that lung B cells are able to capture HDM antigens. Following challenge and sensitization with HDM-AF647, 3.4–5.2% of lung B cells, as well as a substantial proportion (7.4–21.1%) of lung dendritic cells, but only a few lung CD4+ T cells (0.3–1.5%), stained positive for HDM-AF647 after 24 hours.
HDM-AF647 was also taken up by B cells from MD4 mice with rearranged heavy and light chain transgenes encoding for a hen egg lysozyme-specific monoclonal antibody, indicating that the process of HDM uptake and antigen presentation “is not restricted to rare B cells carrying HDM-specific B cell receptors,” say Sallusto and team.
The researchers also showed that lung B cells taken from HDM-sensitized mice were able to present HDM antigens and stimulate cytokine production by CD4+ CD44+ T cells. The ability of the B cells to induce the production of interleukin (IL)-4, -5, and -13 was comparable to that of dendritic cells, but unlike dendritic cells, B cells were not able to restimulate IL-17 release from CD4+ cells.
These results show that “B cells efficiently take up HDM antigens independently of their B cell receptor specificity and serve as potent antigen presenting cells,” write the researchers.
They explain that in experiments conducted using mice with major histocompatibility complex-II expression restricted to the B-cell lineage, B cells were unable to initiate Th2 responses on their own, but had an “unexpected role” of priming naïve CD4+ T cell precursors to differentiate into Th1 and Th17 subsets.
Taken together, the study findings “reveal new mechanisms leading to initiation and exacerbation of allergic response that may have implications for designing new therapeutic strategies to combat house dust mite allergy,” concludes the team in the Journal of Allergy and Clinical Immunology.
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