Title:

Understanding Antibody Production in Waldenström’s Macroglobulinemia

Waldenström’s Macroglobulinemia (WM) is a rare non-Hodgkin’s lymphoma characterized by the overproduction of circulating antibody, immunoglobin M (IgM). This blood cancer affects white blood cells like lymphoplasmacytic and plasma cells. WM is considered a severe malfunction of the antibody producing system in our bodies; this results in patients not being able to change their antibody isotype from IgM to IgA, IgG, or IgE. The change of antibody isotype is known as class switch recombination (CSR). White blood cells undergo CSR to produce antibodies that are better suited to fighting the diseases and infections our immune system encounters. The reason behind impaired CSR in WM is yet to be discovered. In this study, we aim to investigate the ability of WM cells to undergo class switching when subjected to various cytokine cocktails while simultaneously inhibiting the Hedgehog signaling transcription factor GLI2 in vitro. GLI2 is a modulator of IgM; therefore, using the GLI2 antagonist GANT61 will reduce the secretion IgM from WM cells and will promote class switching while combined with cytokines like TGF-β, CD40L, BAFF, and IL4. Post incubation of WM cells with different cytokine cocktails, with and without GANT61, samples were collected, and flow cytometry was performed to detect which antibody isotype is present on the surface of the cells. Due to severe procedural errors no conclusion was drawn from the experiment; this study will be performed again to assess the nature of class switching in WM cells.

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