Activation of human B cells with the Moraxella catarrhalis IgD-binding protein MID

Sammanfattning: Moraxella catarrhalis is a respiratory tract pathogen that causes significant health problems, including acute otitis media in children, lower respiratory tract infections in adults and the elderly and sinusitis in both children and adults. The interest in M. catarrhalis bacteria has increased over the past 20 years, both because of the emergence of the bacteria as a human pathogen and because of its increasing prevalence of antibiotic resistance. For these reasons, attention has been focused on the importance of a viable vaccine against M. catarrhalis. The outer membrane protein MID (Moraxella IgD-binding protein) from M. catarrhalis is one of the potential candidates. In this matter, knowledge of the interactions of potential candidates (i.e. MID) with human cells is of much significance. MID has the unique ability to bind to IgD-positive B lymphocytes (B cells). These cells are key agents in the immune system, with their specific role as immunoglobulin- (Ig) secreting cells. This ability is crucial for recognising and responding to external antigens, and is the underlying factor for adaptive immunity. In this thesis the interactions between MID and human B cells have been investigated. The potential of the MID protein to function as a B-cell activator has been studied using both primary B cells and different B cell lines. We show that MID has the capacity to activate peripheral blood and tonsillar B cells, to both proliferation and IL-6 secretion. The importance of B cell surface molecules for MID binding and activation of the cells has also been studied. Results presented here demonstrate that the two B cell co-receptors, CD19 and CD21, are highly important for MID-induced activation. We show that for a B-cell response in young individuals the CD19 molecule must be available. Furthermore, information from studies of different B cell lines indicates that the CD21 molecule is important in mediating a successful IgD-binding, although MID-binding to CD21 alone is not sufficient to induce cell activation. Moreover, we present data that MID-induced activation of tonsillar B cells is inhibited by Alpha-1-antitrypsin (AAT), a common serine inhibitor in plasma and tissues.