Naturally Occurring Autoantibodies in Mediating Clearance of Senescent Red Blood Cells

  • Hans U. Lutz
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 750)


Germline-encoded naturally occurring autoantibodies (NAbs) developed about 400 to 450 million years ago to provide specificity for clearance ofbody waste in animals with 3 germ layers. Such NAbs became a necessity to selectively clear aged red blood cells (RBC) surviving 60 to 120 d in higher vertebrates. IgG NAbs to senescent RBC are directed to the most abundant integral membrane protein, the anion-transport protein or band 3 protein, but only bind firmly upon its oligomerization, which facilitates bivalent binding. The main constituent of RBC, the oxygen-carrying hemoglobin, is susceptible to oxidative damage. Oxidized hemoglobin forms hemichromes (a form of aggregates) that bind to the cytoplasmic portion of band 3 protein, induces their clustering on the cytoplasmic, as well as the exoplasmic side and thereby provides the prerequisites for the low affinity IgG anti-band 3 NAbs to bind bivalently. Bound anti-band 3 NAbs overcome their low numbers per RBC by stimulating complement amplification. An affinity for C3 outside the antigen binding region is responsible for a preferential formation of C3b2-IgG complexes from anti-band 3 NAbs. These complexes first bind oligomeric properdin, which enhances their affinity for factor B in assembling an alternative C3 convertase.


Alternative Complement Pathway Bivalent Binding Senescent Erythrocyte Mediate Clearance Congenital Dyserythropoietic Anemia Type 
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Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  • Hans U. Lutz
    • 1
  1. 1.Institute of Biochemistry, Swiss Federal Institute of TechnologyETH HönggerbergZurichSwitzerland

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