Heme drives proliferation of naïve and memory B cells by enhancing G1/S phase cell cycle progression

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B628
Abstract ID: 6237

Presenting Author:
Herbey O Padilla-Quirarte , Heme drives proliferation of naïve and memory B cells by enhancing G1/S phase cell cycle progression at Emory Univ. Sch. of Med.

Abstract:

Iron is elemental for multiple cellular biochemical processes like DNA synthesis and energy generation and recently the role of it has been reported to be important for B cells to produce antibodies. B cell differentiation to plasma cells is tightly regulated with cell division, where several epigenetic and metabolic changes occur, as cell divides. RNAseq performed on iron/heme treated differentiating naïve B cells (nB) after activation with LPS showed that heme regulated cell cycle, proliferation, and DNA synthesis genes when compared to cells treated with vehicle. Genes like Cdkn1a, Cdkn2a and Cdkn2b, which codify for cyclin-dependent kinase inhibitors that control the retinoblastoma protein activity were DEG with heme treatment, as was as Rb1 gene itself. To understand better how heme regulates cell division, ex vivo cultures of naïve and memory B cells (MBC) were stained with the cell tracing dye CTY and followed activation after T dependent or T independent activating signals. Both nB and MBC showed increased proliferative capacity against two antigens when treated with heme that correlated with higher levels of replicating cells as BrDu stain indicated. Furthermore, the Rb protein levels of total form were decreased on nB treated with heme compared to vehicle control. In summary, this work provides more insight to the mechanism of heme promoting plasma cell differentiation by enhancing the proliferation by enhancing G1/S phase cell cycle progression.