Time course of IgM antibodies which block anti-myelin basic protein IgG antibodies associated with development of experimental autoimmune encephalomyelitis in rabbits

Several authors have demonstrated the presence in normal sera of antibodies that inhibit binding of a variety of autoantibodies. These inhibitory or b locking antibodies are generally considered to play a role in humoral self- tolerance. We examined sera from normal rabbits and from rabbits with exper imental autoimmune encephalomyelitis (EAE). in search for antibodies capabl e to inhibit reactivity of autoantibodies directed to myelin basic protein (MBP). Rabbits injected with bovine myelin in complete Freund's adjuvant (E AE rabbits) or with adjuvant alone (control rabbits) were bled at various i ntervals post-injection. Sera were subjected to chomatography on a protein A-Sepharose column. retained and nonretained fractions were collected. and ability of these fractions to block reactivity of affinity-purified anti-MB P IgG-antibodies was analyzed by immunoblot technique. Protein A nonretaine d fraction from control rabbits inhibited anti-MBP IgG reactivity to the sa me degree at all intervals tested, whereas the same fraction from EAE anima ls showed an increase in inhibitory activity after induction of the disease . This inhibitory activity declined with the onset of clinical symptoms, an d remained low in rabbits that did not recover from the disease. In contras t. the inhibitory activity remained at maximum value in EAE rabbits with sp ontaneous remission of clinical symptoms. We showed that the inhibitory act ivity is due to IgM-antibodies, and discussed the role of these antibodies in the development of EAE. (C) 2001 Elsevier Science B.V. All rights reserv ed.