Innate immune responses provoke the accumulation of leukocytes at sites of 
inflammation. In addition to monocytes and granulocytes, B cells also 
participate in antimicrobial innate immune responses; however, the mechanisms 
for accumulation of B cells to sites of inflammation are not well understood. To 
study B cell accumulation following systemic inflammation, we used a model 
synthetic ligand that stimulates a specific pattern recognition molecule, 
nucleotide-binding oligomerization domain-containing protein 1 (Nod1). Upon 
exposure to Nod1 agonists, both B cells and neutrophils rapidly accumulate 
within the spleen, and dendritic cells migrate into the periarterial lymphoid 
sheath. Nod1 stimulation led to a marked increase in several chemokines within 
the spleen, including CXCL13, CCL2, and CCL20. Whereas the lymphotoxin pathway 
was critical for the induction of the B cell chemoattractant CXCL13 in response 
to Nod1 agonists, B cell accumulation within the spleen following Nod1-induced 
systemic inflammation was independent of the lymphotoxin pathway. In contrast, a 
CCR6/CCL20 chemokine loop instructed rapid increase of B cells in the spleen in 
response to systemic administration of Nod1 agonists in a TNF-α-dependent 
manner. Moreover, CCR6 was required to regulate Nod1-mediated B cell responses. 
These results reveal a novel mechanism of B cells during inflammation and shed 
light on how B cells participate in innate immune responses to microbial 
stimulation.