# Distinct roles for LTalpha3 and LTalpha1beta2 produced by B cells contribute to their multi-faceted impact on ileitis

## TL;DR

B cells help control ileitis through multiple mechanisms, including producing protective antibodies and different forms of lymphotoxin.

## Contribution

The study reveals distinct roles of LTα3 and LTα1β2 from B cells in managing ileitis and weight loss.

## Key findings

- B cell-derived secretory IgA protects against ileal inflammation.
- LTα1β2 from B cells drives TLS formation but does not prevent weight loss.
- LTα3 protects against weight loss by counteracting TNF-driven cachexia.

## Abstract

B lymphocytes may facilitate chronic inflammation through antibody production or secretion of cytokines, including lymphotoxin (LT)-a1b2 associated with development of lymphoid tissue. Tertiary lymphoid structures (TLS) characterize human and murine ileitis by suppressing outflow from the ileum. Here, we show that B cell-derived secretory IgA protected against ileal inflammation, whereas B cell-derived LTa guarded against ileitis-associated loss of body mass. We initially hypothesized this protection resulted from formation of TLS that suppressed lymphatic outflow and thereby restrained systemic spread of inflammatory signals, but B cell-selective deletion of LTb did not exacerbate weight loss, despite eliminating TLS. 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 for protecting against weight loss in the presence of TNF.