B cells promote Th2 cytokine production and pathophysiology during chronic allergic lung disease

The role of B cells in chronic allergic lung disease, or asthma, remains controversial. Our goal in these studies was to characterize the role of B cells in a clinically relevant murine model of chronic allergic lung disease, with a focus on B cell antigen presentation. To this end, mice were chronically challenged (eight times total) with cockroach allergen extract, and the lung B cell response was determined. Chronic allergen challenge resulted in the accumulation of large numbers of B cells to the lungs, which expressed MHC II and the costimulatory molecules CD40, CD80 and CD86. In cocultures with CD4+ T cells, purified lung B cells promoted T cell proliferation and antigen‐specific Th2 cytokine production (IL‐4, IL‐5, and IL‐13, but not IFNg). B cell −/− mice (muMT) had attenuated airway hyperresponsiveness, and decreased mucus hypersecretion. The levels of Th2 cytokines in the lungs of B cell −/− mice were decreased relative to B cell sufficient controls, demonstrating that B cells play a role at promoting pathophysiology and Th2 cytokine responses in vivo. Repopulation of B cells into muMT mice significantly increased CD4 T cell responses in the lungs and increased mucus. Collectively, these results suggest that B cell antigen presentation plays an important role in promoting Th2 cytokine and pathophysiology in allergic lung disease. (NIH‐ HL031963 , HL059178 , and T32HL07749)