B-CELL AUTOIMMUNITY TO ACETYLCHOLINE-RECEPTOR AND ITS SUBUNITS IN LEWIS RATS OVER THE COURSE OF EXPERIMENTAL AUTOIMMUNE MYASTHENIA-GRAVIS

Experimental autoimmune myasthenia gravis (EAMG) is induced by a singl e injection of acetylcholine receptor (AChR) with complete Freund's ad juvant and represents a useful animal model for studying the mechanism s by which autoimmune responses to AChR and its subunits are coupled t o the development of human myasthenia gravis. Using an immunospot assa y, we enumerated cells secreting IgG antibodies against Torpedo AChR a nd the alpha-, beta-, gamma- and delta-subunits of Torpedo AChR in lym ph nodes, spleen and thymus from Lewis rats over the course of EAMG. C ells secreting IgG antibodies to AChR and to all four subunits were de tected at higher numbers in the three immune organs in EAMG compared t o controls. Numbers were highest in lymph nodes followed by spleen and thymus. Cells secreting IgG antibodies against native AChR were alway s higher than those against individual subunits. The immunogenicity be tween the four subunits did not differ, with the exception that the al pha-subunit induced a slightly higher B cell response in thymus and ly mph nodes. The patterns of B cell responses were similar when analyzed over the course of EAMG from week 2 to week 5, and there was no restr iction of the B cell repertoire early in EAMG. Anti-AChR and anti-subu nit antibody-secreting cells were also detected in control animals imm unized with adjuvant only, but at numbers which were much lower, and w hich were within the same level as numbers of cells secreting IgG anti bodies to the control antigen myelin basic protein, probably reflectin g naturally occurring autoimmune B cells.