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This is of importance because the gut is the largest reservoir of IgA in the body, which maintains gut homeostasis in part by regulating the composition of the gut microbiota. This was addressed by development of a prolonged B cell depletion model using human CD20 transgenic mice and B cell depletion with the anti-human CD20 antibodies rituximab, a humanized mouse monoclonal, and 2H7, the mouse precursor to ocrelizumab. Both antibodies depleted B cells in the spleen, mesenteric lymph nodes, small intestine, and large intestine, with 2H7 being more efficient. Because gut IgA+ antibody secreting cells (ASC) are poorly defined a flow cytometry strategy was developed using differential expression of IgA and Ki-67 by Blimp1+ cells that identified four IgA-ASC subsets across a developmental spectrum. Neither antibody was efficacious in depleting of any IgA-ASC subset in the intestines. Consequently, fecal IgA levels and percentage of IgA-bound fecal microbes were unaltered. Cumulatively, these studies demonstrate that prolonged B cell-depletion did not substantially impact IgA levels nor overall gut health, providing important insight into the safety profile of B cell depletion drugs.<\/jats:p>","DOI":"10.1093\/jimmun\/vkae046","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:36:45Z","timestamp":1741221405000},"page":"780-794","source":"Crossref","is-referenced-by-count":2,"title":["Gut IgA-antibody secreting cells segregate into four Blimp1+ subsets based on differential expression of IgA and Ki-67 and are retained following prolonged \u03b1CD20 B cell depletion in mice"],"prefix":"10.1093","volume":"214","author":[{"given":"Savannah D","family":"Neu","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Medical College of Wisconsin , Milwaukee, WI,","place":["United States"]},{"name":"Versiti Blood Research Institute , Milwaukee, WI,","place":["United 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