PubMed · 8211092
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I L Weissman, M D Cooper. 1993. How the immune system develops.. https://doi.org/10.1038/scientificamerican0993-64
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The complex family of human IgG Fc receptors show a wide cellular distribution and a strong functional heterogeneity. To date, eight different genes that are transcribed into at least 12 different mRNAs have been recognized. Although corresponding products have been identified for only some of the transcripts, in vivo at least six different Fc gamma R isoforms are shown to be present on the surface of all kinds of leukocytes. Upon interaction with immunoglobulin, Fc gamma R mediate a variety of biological responses such as phagocytosis, endocytosis, release of inflammatory mediators, and antibody-dependent cellular cytotoxicity. One of the main questions in Fc gamma R research is determining the specific relationship between a particular Fc gamma R isoform and a particular effector mechanism. The availability of the cDNA and genomic clones corresponding to the different isoforms, combined with different gene transfer systems in vitro and in vivo and the recently developed procedure of gene knockout by homologous recombination, allows the generation of stably transfected cell lines and transgenic animals that express one particular Fc gamma R isoform. These model systems enable us to study the function of a particular Fc gamma R isoform in the context of a particular cell type in vitro and in the context of the intact immune system in vivo.
It is well-established that multiple sclerosis (MS) in Caucasians is associated with HLA-DR2. A number of studies have indicated that other genes may also influence the susceptibility to MS. Gm allotypes of immunoglobulin (Ig) genes have been reported to be associated with MS several times, but the described associations differ and have not been confirmed. We report here the results of restriction fragment length polymorphisms (RFLP) analysis of the constant gene regions of immunoglobulin gamma (IgG C) 1, 2 and 3 in MS patients and controls, using the restriction enzymes TaqI, PvuII and BstEII. No significant differences were observed, regardless of subgrouping of patients according to clinical disease type or HLA class II phenotype. These results are in contrast with a previous study where a BstEII RFLP was found to differ between MS patients and controls. In conclusion, the hypothesis that constant gene segments of the IgG genes confer susceptibility to MS still lacks convincing experimental support.
In this study, we demonstrate the use of oligonucleotide probes to the most VH family-specific framework, the Framework 3 (FR3) gene segment, in the analysis of germline DNA. Compared with the hybridization of restriction enzyme-digested genomic DNA to large, cloned human VH family probes, hybridization with oligonucleotides derived from nucleotides 199 to 258 of the FR3 gene segments both yields less complex patterns and highlights polymorphic variations between individuals. The potentially important role played by amino acid residues encoded by the FR3 gene segment in influencing conformation, antigen binding and affinity of the physically proximal complementarity determining regions (CDRs) suggests FR3 sequence conservation to be biologically significant. Genomic studies combining information from both CDR and framework restriction fragment polymorphisms can prove useful in detecting specific genes and in identifying haplotypes of interest.