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We identify the histone methyltransferase MLL1 as a key target to promote IgA-driven responses. Mll1 was increased in germinal center B cells in gut-associated lymphoid tissues, and Mll1-deficiency led to changes in the histone modification H3K4me3 on key B cell and immune-regulatory genes. Correspondingly, MLL1-deficient B cells had defective germinal centers and IgG1 in response to the helminth Trichuris muris. Yet Mll1f\/fCd23cre\/+ mice expelled worms more rapidly compared to control mice. Accelerated worm clearance correlated with elevated immunoglobulin A (IgA)+ plasma cells, as well as both serum and fecal IgA. RNA-sequencing identified CCR9 as a key MLL1-regulated molecule. As such, Mll1f\/fCd23cre\/+ mice infected with T. muris had increased IgA+CCR9+ PC localized in the large intestine. Regulation of IgA by MLL1 was confirmed beyond T. muris infection. In vitro cultures confirmed Mll1-deficiency increased IgA+ plasma cells in a B cell-intrinsic manner, and IgA production was also increased in Mll1f\/fCd23cre\/+ mice infected with the bacterium Citrobacter rodentium. This study reveals MLL1 as a key target to promote IgA responses to gut-associated infections.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf358","type":"journal-article","created":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T17:13:41Z","timestamp":1772385221000},"source":"Crossref","is-referenced-by-count":0,"title":["MLL1 directs gut-associated antibody responses to helminth and bacterial infections"],"prefix":"10.1093","volume":"215","author":[{"given":"Yan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Monash University , Clayton, Victoria,","place":["Australia"]},{"name":"Immunity Program, Biomedicine Discovery Institute, Monash University , Clayton, Victoria,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clarissa","family":"Chakma","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Monash University , Clayton, Victoria,","place":["Australia"]},{"name":"Immunity Program, Biomedicine Discovery Institute, Monash University , Clayton, Victoria,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4114-5546","authenticated-orcid":false,"given":"Alana","family":"Kirn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Monash University , Clayton, Victoria,","place":["Australia"]},{"name":"Immunity Program, Biomedicine Discovery Institute, Monash University , Clayton, Victoria,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0421-3957","authenticated-orcid":false,"given":"David","family":"Chisanga","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Monash University , Clayton, Victoria,","place":["Australia"]},{"name":"Immunity Program, Biomedicine Discovery Institute, 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Victoria,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9586-6821","authenticated-orcid":false,"given":"Liang","family":"Xie","sequence":"additional","affiliation":[{"name":"Immunity Program, Biomedicine Discovery Institute, Monash University , Clayton, Victoria,","place":["Australia"]},{"name":"Department of Microbiology, Monash University , Clayton, Victoria,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"L\u00f3pez-Ure\u00f1a","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Monash University , Clayton, Victoria,","place":["Australia"]},{"name":"Infection Program, Biomedicine Discovery Institute, Monash University , Clayton, Victoria,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Mileto","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Monash 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