Background: Polyreactive antibodies can efficiently neutralize HIV. Results: Heme induces polyreactivity of a human antibody, which recognizes distinct gp120 clades by an identical binding mechanism. Conclusion: Antigen-binding promiscuity of a polyreactive antibody allows recognition of antigen with high molecular heterogeneity. Significance: Characterization of the interaction of polyreactive antibodies with envelope proteins of HIV reveals novel strategies for control of the virus.

Acute inflammation is the body's response to infection or injury, characterised by the rapid infiltration of polymorphonuclear neutrophils to the site of injury followed by monocytes, which differentiate locally into macrophages. The latter are essential for the removal of effete neutrophils and provided that the harmful agent is eliminated, removal of neutrophils will lead to the resolution of inflammation. Perturbations in this process result in the persistence of inflammation and close control of pathways associated with resolution are necessary to avoid chronic inflammation, autoimmunity, or both. As our understanding of these processes increase, drugs able to trigger pro-resolution pathways may represent an effective strategy for treating chronic inflammatory diseases.

Background: Normal immune repertoires have a fraction of cofactor-binding antibodies. Results: Heme exposure results in acquisition of reactivity to gp120 HIV-1 in 24% of antibodies in a seronegative immune repertoire; these antibodies have less mutated variable regions. Conclusion: Human immune repertoires contain high frequency of antibodies with cofactor-induced antigen specificities. Significance: This work enhances understanding of molecular features of heme-sensitive Abs and their contribution to diversification of the immune repertoires.