Background-Recruitment of antigen-specific Th2 cells into the lung is critical for the development of allergic airway inflammation. Although CCR4 and CCR8 are preferentially expressed on Th2 cells and CCR4, CCR8 and CXCR3 ligands are increased in asthma, the specific relative contribution of these receptors to antigen-specific Th2 cell trafficking into the allergic lung is not known.
SUMMARYContact skin immunization of mice with reactive hapten antigen and subsequent airway challenge with the same hapten induces immediate airflow obstruction and subsequent airway hyperreactivity (AHR) to methacholine challenge, which is dependent on B cells but not on T cells. This responsiveness to airway challenge with antigen is elicited as early as 1 day postimmunization and can be adoptively transferred to naı¨ve recipients via 1-day immune cells. Responses are absent in 1-day immune B-cell-deficient JH -⁄ -mice and B-1 B-cell-deficient xid male mice, as well as in recipients of 1-day immune cells depleted of cells with the B-1 cell phenotype (CD19 + B220 + CD5 + ). As B-1 cells produce immunoglobulin M (IgM), we sought and found significantly increased numbers of anti-hapten IgM-producing cells in the spleen and lymph nodes of 1-day immune wild-type mice, but not in xid mice. Then, we passively immunized naive mice with anti-hapten IgM monoclonal antibody and, following airway hapten challenge of the recipients, we showed both immediate airflow obstruction and AHR. In addition, AHR was absent in complement C5 and C5a receptor-deficient mice. In summary, this study of the very early elicited phase of a hapten asthma model suggests, for the first time, a role of B-1 cells in producing IgM to activate complement to rapidly mediate asthma airway reactivity only 1 day after immunization.
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