Anti-IGHM monoclonal antibody

Immunoglobulins loci in mammals are well known to be organized within a translocon, however their origin remains unresolved. Four of the five classes of immunoglobulins described in humans and rodents (immunoglobulins M, G, E and A-IgM, IgG, IgE and IgA) were found in marsupials and monotremes (immunoglobulin D-IgD was not found) thus showing that the genomic structure of antibodies in mammals has remained constant since its origin. We have recently described the genomic organization of the immunoglobulin heavy chain locus in reptiles (IGHM, IGHD and IGHY). These data and the characterization of the IGH locus in platypus (Ornithorhynchus anatinus), allow us to elucidate the changes that took place in this genomic region during evolution from reptile to mammal. Thus, by using available genome data, we were able to detect that platypus IGH locus contains reptilian and mammalian genes. Besides having an IGHD that is very similar to the one in reptiles and an IGHY, they also present the mammal specific antibody genes IGHG and IGHE, in addition to IGHA. We also detected a pseudogene that originated by recombination between the IGHD and the IGHM (similar to the IGHD2 found in Eublepharis macularius). The analysis of the IGH locus in platypus shows that IGHY was duplicated, firstly by evolving into IGHE and then into IGHG. The IGHA of the platypus has a complex origin, and probably arose by a process of recombination between the IGHM and the IGHY. We detected about 44 VH genes (25 were already described), most of which comprise a single group. When we compared these VH genes with those described in Anolis carolinensis, we find that there is an evolutionary relationship between the VH genes of platypus and the reptilian Group III genes. These results suggest that a fast VH turnover took place in platypus and this gave rise to a family with a high VH gene number and the disappearance of the earlier VH families. (C) 2009 Elsevier Ltd. All rights reserved.

The only immunoglobulin heavy-chain classes known so far in teleosts have been mu and delta. We identify here a previously unknown class, immunoglobulin zeta, expressed in zebrafish and other teleosts. In the zebrafish heavy-chain locus, variable (V) gene segments lie upstream of two tandem diversity, joining and constant (DJC) clusters, resembling the mouse T cell receptor alpha (Tcra) and delta (Tcrd) locus. V genes rearrange to (DJC)(zeta) or to (DJC)(mu) without evidence of switch rearrangement. The zebrafish immunoglobulin zeta gene (ighz) and mouse Tcrd, which are proximal to the V gene array, are expressed earlier in development. In adults, ighz was expressed only in kidney and thymus, which are primary lymphoid organs in teleosts. This additional class adds complexity to the immunoglobulin repertoire and raises questions concerning the evolution of immunoglobulins and the regulation of the differential expression of ighz and ighm.