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Connexin 43 communication channels in follicular dendritic cell development and in follicular lymphomas
Hajnalka Rajnai1, Ivett Teleki1, Gergo Kiszner1
11st Department of Pathology and Experimental Cancer Research, 1085 Budapest, Hungary.
Insights
Connexin 43 (Cx43) gap junctions are vital for follicular dendritic cell (FDC) development and function in germinal centers. Cx43 supports FDC persistence in follicular lymphomas but does not drive tumor progression.
Area of Science:
- Immunology
- Cell Biology
- Cancer Biology
Background:
- Follicular dendritic cells (FDCs) utilize connexin 43 (Cx43) gap junctions for metabolic coupling, supporting B cell selection and maturation in germinal centers.
- In follicular lymphomas, B cells evade apoptosis, and FDCs exhibit abnormal development, suggesting a role for Cx43 in this pathology.
Purpose of the Study:
- To investigate the role of Cx43 channels in reactive FDC development and their involvement in follicular lymphomas.
- To determine the correlation between Cx43 expression, FDC density, and B cell proliferation in both reactive and malignant lymphoid tissues.
Main Methods:
- In vitro culture of FDC-B cell clusters treated with Gap27 peptide to inhibit Cx43 channels.
- Ex vivo analysis of Cx43 protein levels and FDC density in reactive germinal centers and follicular lymphoma tissues.
- Assessment of B cell proliferation in relation to Cx43 expression and lymphoma characteristics.
Main Results:
- Gap27 peptide treatment impaired FDC-B cell cluster formation and survival in vitro.
- Cx43 protein levels correlated with FDC density in reactive germinal centers and follicular lymphomas.
- Cx43 upregulation was observed in developing/degrading FDC, but the inverse correlation with B cell proliferation seen in reactive germinal centers was absent in follicular lymphomas.
- Cx43 levels did not correlate with lymphoma grade or bone marrow involvement.
Conclusions:
- Cx43 channels are crucial for FDC development and maintenance within germinal centers and follicular lymphomas.
- Cx43 plays a role in FDC persistence in follicular lymphomas but does not appear to influence tumor progression or aggressiveness.
Abstract:
Follicular dendritic cells (FDC) show homo- and heterocellular metabolic coupling through connexin 43 (Cx43) gap junctions and support B cell selection and maturation in germinal centers. In follicular lymphomas B cells escape apoptosis while FDC develop abnormally. Here we tested Cx43 channels in reactive FDC development and follicular lymphomas. In culture, the treatment of FDC-B cell clusters (resembling to "ex vivo" germinal centers) with Gap27 peptide, mimicking the 2nd extracellular loop of Cx43 protein, significantly impaired FDC-B cell cluster formation and cell survival. In untreated cultures of intact clusters, cell proliferation showed a moderate reduction. In tissues, Cx43 protein levels run parallel with the density of FDC both in reactive germinal centers and in malformed follicles of follicular lymphomas and showed strong upregulation in newly generated and/or degrading bi-/multinuclear FDC of rudimentary processes. However, the inverse correlation between Cx43 expression and B cell proliferation seen in reactive germinal centers was not detected in follicular lymphomas. Furthermore, Cx43 levels were not associated with either lymphoma grade or bone marrow involvement. Our results suggest that Cx43 channels are critical in FDC and "ex vivo" germinal center development and in the persistence of FDC in follicular lymphomas but do not affect tumor progression.
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