Demonstration of light chain mRNA in Hodgkin's disease

Abstract

The lineage of Hodgkin and Reed-Sternberg cells is still unclear. Detection of both immunoglobulin light chains in Hodgkin and Reed-Sternberg cells by immunohistochemistry is a well-known phenomenon. However, up to now, in situ hybridization techniques have failed to demonstrate light chain messenger(m) RNA in Hodgkin and Reed-Sternberg cells. In this investigation, we have analysed 26 cases of Hodgkin's disease (nodular lymphocyte predominant Hodgkin's disease, mixed cellularity, and nodular sclerosis type) using digoxigenin-labelled oligonucleotide probes for kappa and lambda light chains by in situ hybridization. In nearly half of the cases of nodular lymphocyte predominant Hodgkin's disease and in one case of mixed cellularity type, mRNA for only one light chain could be clearly demonstrated in the lymphocytic and histiocytic cells, Hodgkin, and Reed-Sternberg cells. These results support the idea that at least some cases of Hodgkin's disease are B-cell neoplasms.

Expression pattern of intracellular leukocyte-associated proteins in primary mediastinal B cell lymphoma

“…23,24 The former is almost specific, 25 whereas FIG1 protein can be found in a significant minority of non-mediastinal diffuse large B cell lymphoma 6,23,25 Reed-Sternberg cells in the great majority of the cases of classical Hodgkin's disease are also clearly of B lymphoid origin but they show extensive disruption of the 'B cell program', that is, loss of B cell-associated molecules. [26][27][28][29][30] We recently provided further evidence for this phenomenon in an immunohistologic labeling study of five B cell-associated intracellular signaling molecules (BLNK, Syk, PLC-g2, Fyn and Lyn) in Hodgkin's disease. 8 These molecules are expressed in normal B cells, 12 but we noted that Reed-Sternberg cells in the great majority of cases lacked BLNK, Syk and PLC-g2, and that Fyn and Lyn were present in a substantial number.…”

Down-regulation of BOB.1/OBF.1 and Oct2 in classical Hodgkin disease but not in lymphocyte predominant Hodgkin disease correlates with immunoglobulin transcription

“…Furthermore, all previous in situ hybridization studies that were applied to LPHD cases were restricted to IgL chains. 3,[26][27][28] To clarify how frequently and at which level the immunoglobulin synthesis in the tumor cells of cHD is disturbed, it is necessary to obtain representative results to investigate the same collection of cases not only for the immunoglobulin light chain types and but also for the heavy chain isotypes Ig, Ig␦, and Ig␥ at the protein and RNA levels. Another important reason for studying cases of cHD for both immunoglobulin proteins and immunoglobulin transcripts in parallel lies in the fact that the immunostaining of paraffin sections for immunoglobulin protein often leads-due to uptake of immunoglobulin from interstitial fluids-to a falsely positive labeling of larger cells.…”

Epigenetic silencing of the immunoglobulin heavy-chain gene in classical Hodgkin lymphoma-derived cell lines contributes to the loss of immunoglobulin expression

“…Hodgkin lymphoma (cHL) are unable to produce both immunoglobulin (Ig) light (L) chain [1][2][3] and heavy (H) chain, 4 despite the presence of clonally rearranged IgL and IgH genes. 4,5 Two explanations have been considered so far for this Ig down-regulation: "crippling" mutations within the transcription control regions and/or in the coding sequence 6 ; and the absence or diminished production of critical transcription factors.…”