Single cell sequencing data on ileum and mesentery tissue from Crohn's disease patients

B lymphocytes may facilitate chronic inflammation through antibody production or secretion of cytokines, including lymphotoxin (LT)-a and -b associated with development of lymphoid tissue. Tertiary lymphoid structures (TLS) characterize human and murine ileitis by suppressing outflow from the ileum. Here, we unraveled disparate roles for B cells in chronic ileitis driven by the cytokine TNF. B cell-derived secretory IgA protected against ileal inflammation, whereas B cell-derived LTa guarded against ileitis-associated loss of body mass. This protection was not due to formation of TLS, as we initially hypothesized, because enhanced weight loss did not emerge when TLS were eliminated during ileitis due to B cell-selective deletion of LTb. Instead, weight loss driven by the cachectic cytokine TNF was exacerbated when LTa3, another ligand for TNF receptors, was selectively neutralized. Thus, B cells’ multi-faceted impact on ileitis includes generating secretory IgA, expressing LTa1b2 to drive formation of TLS, and producing LTa3 to protect against weight loss in the presence of TNF.