ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Humoral immunity is critical to provide protection against a wide range of pathogens. The mechanisms underpinning the tailoring of appropriate antibody responses to helminth infections are not well understood, but responses leading either to resistance or susceptibility to infection are known to be differentially regulated by cytokines secreted by Th cell subsets. Here, we study the role of MLL1, a methyltransferase which regulates histone H3 lysine 4 methylation. In non-B immune cells, MLL1 helps tailor cell differentiation in response to Th2 vs Th1 cell-biased microenvironmental signals. While it is known that MLL1 is required for B cell development, its role in tailoring B cell differentiation during humoral responses has not yet been determined. Therefore, we sought to identify the role of MLL1 in B cell differentiation to helminth infection. Mll1^f/fCd23^Cre/+ mice, in which Mll1 was conditionally deleted in mature B cells, were infected with either low dose or high dose Trichuris muris to induce Th1-mediated or Th2-mediated B cell response, respectively. Worm expulsion in Mll1^f/fCd23^Cre/+ mice occurred more rapidly during Th2-mediated responses to Trichuris muris infection, compared to control mice. Furthermore, MLL1 deletion led to decreased germinal centre B cells, correlating to increased Cmah and Chst1 expression, identified by RNA-sequencing. In comparison, there was no change in worm expulsion or germinal centre formation in Th1-mediated responses to low dose helminth infection. While antibody production occurred during early timepoints post-infection, T. muris-specific IgG1 reduced significantly during the late stage of high dose-induced Th2-bias B cell response in Mll1^f/fCd23^Cre/+ mice. Surprisingly, the absence of MLL1 did not alter H3K4 methylation, and thus we are currently investigating the role of other target histone modifications mediated by MLL1 during helminth infection. In summary, our results demonstrated that MLL1 plays a crucial role in B cell differentiation during the Th2-cell biased response.