To study the involvement of B cells in the immune response to
acetylcholine receptor (AChR), B-cell-deficient (mu mutant) and control wild-type C57BL/6 mice were immunized with AChR and assessed for clinical and immunopathological manifestations of
experimental autoimmune myasthenia gravis (EAMG). The mu mutant mice failed to generate anti-AChR
antibodies and were completely resistant to the induction of EAMG. However, mu mutant mice developed clinical EAMG when
antibodies to the AChR main immunogenic region were passively transferred. Further, the in vivo expansion of lymph node cells after AChR immunization was greatly impaired in mu mutant mice. The mu mutant mice gave an effective in vitro T cell immune response to the immunodominant pathogenic AChR alpha chain
peptide 146-162 (alpha 146-162) and to the whole AChR
protein when tested on day 90 after immunization with AChR, whereas the response to both AChR and its alpha 146-162
peptide was reduced when tested on day 7 after immunization. The in vitro production of IFN-gamma and
IL-2 by AChR-specific and alpha 146-162
peptide-specific lymphocytes was lower in mu mutant mice. The AChR immune mu mutant T cells proliferated and produced IFN-gamma when AChR or alpha 146-162
peptide was presented by wild-type irradiated AChR-primed antigen-presenting cells (APCs). This indicates that B cells are important in the processing and presentation of AChR dominant
peptide in vitro during the initial immune response to AChR. However, APCs of non-B-cell lineage are sufficient to process AChR and prime the T cells to AChR dominant
T cell epitope peptides.