|Lange, M - U. MISS. MEDICAL CTR.|
|Lobb, C - U. MISS. MEDICAL CTR.|
Submitted to: Journal of Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 25, 2009
Publication Date: May 1, 2009
Citation: Lange, M.D., Waldbieser, G.C., Lobb, C.J. 2009. Patterns of Receptor Revision in Immunoglobulin H Chains of A Teleost Fish. Journal of Immunology 182:5605-5622. Interpretive Summary: In addition to its commercial importance in aquaculture, the channel catfish (Ictalurus punctatus) is a powerful model for identifying immune mechanisms in lower vertebrates and elucidating the evolution of the vertebrate immune system. However, little is known regarding the genetic mechanism underlying the immune pathways in catfish cells. This research was performed to identify unique mechanisms that contribute to variation in immunoglobulin molecules. The results showed that catfish B lymphocytes can undergo a type of immunoglobulin receptor editing termed ‘receptor revision’, which can provide variation within clonally expanded B-cells. Increased knowledge of the mechanisms controlling catfish immunity will improve our ability to identify catfish with superior immune responses.
Technical Abstract: H chain cDNA libraries were constructed from the RNA derived from seven different organs and tissues from an individual catfish. The analysis of these libraries has shown that receptor revision occurs within clonally expanded B cell lineages. Revisions represented about 3% of the randomly sequenced clones. VH members from the same or different family as that within the recipient were used as revision donors. Within a clonal set different independent revisions as well as sequential revisions (wherein a primary revision had undergone a secondary revision) were identified, and their presence was confirmed in different tissues. Somatic mutation had occurred both before and after receptor revision in various clonal sets. Murine statistical models of recombination signal efficiency correctly predicted signal sequences in functional catfish germline V region gene segments, and these models were used to evaluate cryptic recombination signal sequences (cRSS) within recipients targeted for revision. These results identified significant donor and recipient cRSS pairs that would allow seamless revisions to occur via hybrid joint formation. The heptamers of the cRSS pairs were located at different locations within the coding region, and different revisions resulted in the replacement of one or both CDR as well as revisions which replaced the upstream untranslated region and leader. These studies provide phylogenetic evidence that receptor revision occurs in mature B cells and supports the hypothesis that receptor revision provides an additional level of somatic H chain diversification as well as a CDR-independent mechanism that can alter VH promoter-regulated Ig expression.