Human IgM monoclonal antibodies block HIV-transmission to immune cells in cervico-vaginal tissues and across polarized epithelial cells in vitro

The importance of natural IgM antibodies in protection against infections is still emerging and these antibodies have a potential role in the maintenance of homeostasis through clearance of apoptotic bodies, complement-dependent mechanisms, inflammation and exclusion of misfolded proteins. Natural IgM act as a first line of defence against unknown hazardous factors and are present in most vertebrates. We investigated the functional capacity of anti-HIV-1 IgM monoclonal antibodies, from a combinatorial Fab library derived from healthy individuals, and evaluated their protective role in inhibiting HIV-1 in vitro when passing across the human mucosal epithelial barrier. Primary HIV-1 isolates were efficiently transmitted over the tight polarized epithelial cells when added to their apical surface. Efficient inhibition of HIV-1 transmission was achieved when anti-HIV-1 IgM monoclonal antibodies were added to the basolateral side of the cells. Two of these human IgM MoAbs had the ability to neutralize HIV and reduced infection of dendritic cells in primary cervico-vaginal tissue biopsies in vitro. This indicates a potential role of natural IgM antibodies in the reduction of HIV-1 transmission in mucosal tissues and improve our understanding of how natural IgM antibodies against a neutralizing epitope could interfere with viral transmission

Immunoglobulin A:Molecular mechanisms of function and role in immune defence

Our immune system produces more immunoglobulin A (IgA) than all of the other antibody classes combined. Much of this synthesis is directed towards protection of the mucosal surfaces which form a vast and vulnerable interface with the environment. As the predominant immunoglobulin class at these surfaces, IgA is an important first line of defence. In addition, IgA is also a major serum immunoglobulin. Both monomeric IgA in serum and polymeric secretory forms of IgA mediate a wide range of protective functions through interaction with numerous receptors and other mediators. It is telling that in order to gain better opportunities for invasion, certain pathogens have evolved mechanisms to thwart IgA function. An improved understanding of this multifaceted immunoglobulin is likely to inform strategies for improved treatments for infections and other diseases.</p