Presenting Author: Emily Dennis
, Graduate Student at Univ. of Virginia Sch. of Med.
Abstract:
Ten-Eleven Translocation-2 (TET2) is an epigenetic modifier and potent regulator of immune cells, yet its role in B-1 cell biology is largely unknown. B-1 cells protect against infection and clear apoptotic cells via the production of natural IgM. Our study analyzed B-1 cell subsets from mice with global knockout of TET2 compared to WT controls using flow cytometry to determine the frequency and number of B cell subsets, RNAseq to determine differences in global gene expression as well as BCR repertoire analysis, and ELISA to evaluate plasma IgM levels. Results revealed that mice with TET2-KO had elevated numbers of B-1a and B-1b cells in their primary niche, the peritoneal cavity, as well as in the bone marrow and spleen. Consistent with this finding, circulating IgM was elevated in TET2-KO mice compared to WT. We observed reduced expression in both heavy and light chain immunoglobulin genes, predominantly in B-1a cells from TET2-KO mice compared to WT controls. As expected, IgM was by far the most abundant isotype expressed by genes in B-1 cells. Yet, only in B-1a cells was there a significant increase in the proportion of IgM isotypes in TET2-KO mice compared to WT. Analysis of the CDR3 revealed an increased abundance of replicated CDR3 sequences in B-1 cells from TET2-KO mice, which was more clearly pronounced in B-1a compared to B-1b cells. The results from our study suggest that TET2 may regulate the pool of antigen-specific IgM-producing cells.
Loss of TET2 increases cell number and reduces immunoglobulin CDR3 diversity in B-1 cells
Category
Poster and Podium (Block Symposium)
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Date: May 5 Presentation Time: 11:30 AM to 12:45 PM Room: Exhibit Hall F1