Immunologic Complexity in Neurons

More recent studies analyzing RNA transcripts in dissoThe nervous system and the immune system face a ciated neurons in tissue culture have suggested that common challenge: how to encode for very complex neuronal MHC gene expression may be inducible, by functions using a genome of limited size. A mere 10 the addition of cytokines or by electrical silencing with primary RNA transcripts apparently encode for the comtetrodotoxin (TTX) (Neumann et al., 1995, 1997), but the plexity of the mammalian brain, which has an estimated functional significance of the MHC expression was still 10 neurons. Moreover, each neuron must make thousubject to debate. The conventional wisdom that imsands of specific synaptic connections with other neumune recognition molecules are not present in the CNS rons. In the immune system, where T cells and B cells has now been challenged by the study of Shatz and have nearly unlimited abilities to recognize foreign anticolleagues (Corriveau et al., 1998), whose data suggest gens, the problem of complexity has been solved in the widespread use of a network of MHC I receptor– several ways. Combinatorial diversity through germline ligand systems in electrically active neurons at times rearrangement, somatic mutation, and differential RNA when they are undergoing remodeling and synaptic plassplicing generates receptors that harbor variable reticity. Shatz and colleagues began by searching for gions of immense complexity and specificity. In neugenes regulated by spontaneous neural activity in the rons, although complex patterns of alternative splicing developing visual system. Fetal cats were surgically imof some pre-mRNAs and RNA editing (a special example planted with osmotic minipumps that infused TTX into of somatic mutation at the RNA level) contribute to diverthe lateral ventricle, a method previously determined to sity, immune system–like mechanisms that generate block electrical activity in the lateral geniculate nucleus functional complexity have not been found. The recent (LGN). Surprisingly, an initial dot blot comparison of findings by Corriveau et al. (1998) that neurons regulate RNAs isolated from control and TTX-treated LGNs rethe expression of components of an immune recognition vealed that none of 32 genes known to be regulated by system under physiologically relevant conditions raise neuronal activity in the adult hippocampus are regulated the question of whether neurons use this system in a in the LGN by TTX treatment. This observation suggests classical way to generate diversity, or whether they utithere may be differences in the ways in which gene lize it in a still undiscovered manner. expression is altered by hippocampal activity and acMolecular Basis of Immune Cell Diversity tivity present during embryonic eye-specific layer forDiversity in the immune system is used to establish an mation. essentially unlimited array of complex receptor–ligand In an effort to identify novel genes whose expression interactions. In B cells, the interactions occur between may be regulated by activity during development, Corrithe variable region of antibodies and different antigens.