Analysis of antigen receptor gene and their protein product is frequently used to differentiate monoclonal from polyclonal origin. What is meant by this statement?
Yes. IgH gene analysis and immunohistochemistry are used to determine monoclonality in lymphoid neoplasm.
Antigen receptor genes (heavy and kappa and lambda light chain immunoglobulin, as well as T-cell receptors gamma, delta, alpha and beta) are coded by segmented genes over long distances in their loci. In germline situation (any cell in the body except lymphocytes) the varaible region gene segments V, D and J remain distant. In every B or T lymphocyte, a hierarchic somatic rearrangement occurs at the DNA level, which juxtaposes V(D) and J segments. Thus, each lymphocyte codes a unique antigen receptor gene with a particular V(D)J rearrangement, which has a particular lenght and sequence. Lymphoma originates from the transformation of one lymphoid cell progenitor that proliferates and avoid apoptosis (a clone), and so, all the cells of the lymphoma clone will have the same rearrangement. In normal lymphoid tissues there are as many rearrangements as lymphocytes, determining a polyclonal status. If you use specific primers flanking the V(D)J rearrangement for clonality PCR assays, in a germline situation, you will not have products since the segments are too far apart. In a polyclonal situation you will obtain a lot of bands coming form the different rearrangements. In a clonal situation you will have one or two distinct bands, coming from the common clonal rearrangement.
You can determine clonality by molecular methods (PCR being the present golden method, but also by southern blot) or by flow cytometry or immunohistochemistry, in the case of B cell lymphoma to determine kappa/lambda ratio or by flow cytometry of TCRb in peripheral T cell lymphoma. Hope to have been useful!
All lymphomas and leukemias have a monoclonal cell populations, and you could detect it by PCR of different genes of immunoglogulin family. There are two types of lymphocites B or T, and so there are B or T lymphomas or leukemias. Rearrangements in these genes are different in length among different madure lymphocites, and only If in your tonsil sample or blood sample you have a mainly monoclonal population you could detect it as one or two bands with the same lengh, and these are the gold standard methods to detect monoclonality in lymphoid proliferations.
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