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Immune-type diversity in the absence of somatic rearrangement.

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  • 1Moffitt Cancer Center, Department of Pediatrics, University of South Florida, All Children's Hospital, St. Petersburg 33701, USA.

Abstract

Immunoglobulin gene diversity has been characterized to varying degrees in modern representatives of all of the major radiations of cartilaginous fish. A pattern of overall chromosomal relationships of the various types of joined and unjoined Ig gene clusters is suggested in which the essential features are: (a) both Ig heavy and light-chain gene clusters occur on multiple chromosomes, (b) various classes of Ig are interspersed, (c) not all individual gene loci appear to be closely linked (Fig. 2). The cluster-type Ig gene system appears to be a series of (potentially) individually regulated loci analogous in part to the olfactory receptor gene system (BUCK and AXEL 1991) and markedly distinct from Ig loci in other vertebrate groups and TCR genes. Such a system would be ideal for the creation of variation in both form and function in a large number of clusters while preserving or partially preserving specificity in a number of other gene clusters. The full range of joined genes and the relative number of joined genes (as relates to unjoined genes), have yet to be determined. Nevertheless, a number of conclusions can be drawn: (a) four distinct forms of heavy-chain joining have been identified (VDD-J, VD-DJ, V-D-DJ, and VDJ; Fig. 1); (b) light-chain genes, which possess only two recombining elements, can be found in either unjoined (V-J) or joined (VJ) forms (Fig. 1); (c) physical linkage between individual joined and unjoined genes has not been established, although such investigations have not been pursued in a significantly rigorous manner as to rule out this possibility; (d) joined light-chain genes are expressed and can be somatically mutated. Can germline joining be viewed as an ancestral character? The answer to this needs to be considered in the context of an overall system in which the level of structural and functional redundancy is extremely high. Joining is an adaptation that is unique to multicluster gene families. The phenomenon overcomes the possibility of not generating a specific form of a receptor, a major shortcoming of conventional rearranging Ig and TCR gene systems. The limitation of encoding specific receptors is compensated through large numbers of additional gene clusters that retain the capacity to rearrange and generate new specificities. Commitment of a V region to diverse, fixed specificity also is a property of the NITR genes, which although not related closely to Ig in a structural sense, may reflect an analogous phenomena. The possibility that immune-type diversity is achieved in the absence of somatic rearrangement and that remnants of such systems could be operative in immune recognition in contemporary vertebrates is of extraordinary significance in terms of our overall understanding of the relationships between adaptive and innate immune recognition.

PMID:
10793482
[PubMed - indexed for MEDLINE]
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