Differential neural regulation of a neuromuscular junction‐associated antigen in muscle fibers and Schwann cells

Monoclonal antibodies 3G2 and 4E2 recognize a postsynaptic component of rat neuromuscular junctions. In contrast to many other postsynaptic junctional antigens, expression of this antigen is nerve-dependent: immunoreactivity disappears from junctions following denervation and returns upon reinnervation (Astrow et al., 1992 J. Neurosci. 12:1602-1615). Here we show that the epitope is also expressed by Schwann cells and that this expression is also neurally regulated. Weak mAb 3G2/4E2 immunoreactivity was found in myelinating Schwann cells but was not detected in either nonmyelinating Schwann cells or in terminal Schwann cells at the neuromuscular junction. Following axotomy, immunoreactivity increased in myelinating Schwann cells, and nonmyelinating and terminal Schwann cells became immunopositive. Moreover, the immunoreactivity in terminal Schwann cells revealed their extensive sprouting in response to denervation (Reynolds and Woolf, 1992, J. Neurocytol. 21: 50-66). After nerve regeneration, mAb 3G2/4E2 immunoreactivity in all Schwann cells returned towards normal: it disappeared from terminal Schwann cells, returned to low levels in myelinating Schwann cells, and decreased in nonmyelinating Schwann cells. Immunoblots of axotomized nerve and cultured muscle fibers revealed the same set of immunoreactive bands. Therefore, Schwann cells and muscle fibers share the expression of an epitope that is under neural control, but is regulated differently at each site. In Schwann cells, the presence of the nerve suppresses expression of the epitope, whereas in muscle fibers, the nerve terminal promotes this expression. The differential regulation of mAb 3G2/4E2 immunoreactivity in terminal Schwann cells and muscle fibers suggests that the epitope may be involved in interactions between nerve terminals and these cells.