What is the selective pressure that maintains the gene loci encoding the antigen receptors of T and B cells? A hypothesis.

Abstract

The dominant view is that the gene loci encoding the B cell antigen receptor (BAr) or the T cell antigen receptor (TAr) specify a vast array of combining sites. The 'germline' repertoire is estimated to be > 10(10) by multiplying numbers of subunit complements by DN-region variability. This implies that the germline can be maintained by a selection imposed by all or most of the antigenic universe. Its unchallenged popularity, notwithstanding, this neo-germline view is untenable and hence the need for a competing concept, as presented here. The immunoglobulin (Ig) loci are under a totally different selection from the T loci. The Ig loci are selected upon largely by carbohydrate determinants on pathogens that vary more slowly than the proteins produced by the Ig loci, which are necessary to rid these selective antigens. By contrast, the T loci are selected to recognize the allele-specific determinants on restricting elements encoded in the major histocompatibility complex (MHC). The expression of the germline results in a high copy number (HCN) repertoire; this repertoire is the substrate for 'mutation' that yields the low copy number (LCN) repertoire. For the B cell, these two repertoires interact to optimize the response to the unexpected. For the T cell, only the LCN repertoire is functional. The immunoglobulin (Ig) loci are selected upon as light(L)-heavy (H) pairs; the T loci are selected upon as single units alpha or beta (i.e. the VT-gene segments act as a single pool). This competing concept carries with it many important and testable consequences.