Mesenteric lymph nodes are required for B- but dispensable for local T cell effector responses following Citrobacter rodentium infection in mice.

INTRODUCTION: The intestinal immune system is organized into regionally specialized lymphatic drainage networks that coordinate adaptive responses according to the anatomical site of microbial encounter. During Citrobacter rodentium (C. rodentium) infection in mice, initial colonization occurs in the cecum and proximal colon, where antigen‑presenting cells drain to the corresponding mesenteric lymph nodes (mLN), before the pathogen progresses to dominant attachment in the distal colon at peak infection. These segment‑specific patterns of colonization are matched by segment‑specific lymphatic drainage, such that distinct lymph node compartments support immune priming in different intestinal regions. Understanding how these proximal draining mLN contribute to the development of colonic immunity, despite the later dominance of distal‑colonic infection, remains an important open question.

METHODS: To examine the contribution of the colon‑draining mLN, we surgically removed either the entire mLN chain or only the nodes draining the cecum and colon, followed by C. rodentium infection. Immune responses were analyzed at day 10 and day 18, corresponding to phases in which distal‑colonic colonization dominates.

RESULTS: We found that Th17 effector responses in the colon were maintained independently of the removed mLN, consistent with the fact that local colonic activation is the primary driver of the observed T cell phenotype at these time points. In contrast, B cell differentiation was markedly impaired in mLN‑resected animals: both plasma cell frequencies in the colon and pathogen‑specific serum IgG1 and IgG2a responses were significantly reduced.

DISCUSSION: These findings indicate that, although distal‑colonic T cell activation proceeds locally, effective B cell activation and class switching depend on the presence of the appropriate draining lymph nodes. Overall, this study highlights the segment‑specific organization of intestinal immunity and demonstrates that B cell responses during C. rodentium infection are critically dependent on the lymph nodes draining the cecum and colon, whereas local T cell activation in the distal colon can occur independently of these structures.