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B cells promote Th2 cytokine production and pathophysiology during chronic allergic lung disease
Author(s) -
Lindell Dennis Michael,
Lukacs Nicholas W
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.670.6
Subject(s) - cd80 , immunology , cytokine , cd86 , b cell , medicine , cd40 , t cell , antigen presenting cell , antigen , biology , immune system , cytotoxic t cell , antibody , in vitro , biochemistry
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)