A TNF-α–CCL20–CCR6 Axis Regulates Nod1-Induced B Cell Responses

Abstract

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.

Inflammation rapidly reorganizes mouse bone marrow B cells and their environment in conjunction with early IgM responses

“…Various chemokines have a critical role in B-cell trafficking, both in inflammation and in steady state. 24,25 The CXCR4-CXCL12 axis is particularly important in controlling B-cell homing to and from the bone marrow. 4 It was previously demonstrated that CXCL12 message within the bone marrow decreases 3 days after IFA treatment and this contributed to the loss of bone marrow B cells.…”

Mycobacterium tuberculosis PPE18 protein inhibits MHC class II antigen presentation and B cell response in mice

“…Mature B cells are classified as follicular and marginal zone B cells. Different B cell population were defined as follows, Marginal zone (MZ) B cells as B220 + CD21 hi CD23 int/low , Follicular (FO) B cells as B220 + CD21 int CD23 hi and immature transitional 1 (im/T1) B cells as B220 + CD21 − CD23 − [5A] [15–18]. The mean percentage of immature B cells in mice infected with Msmeg‐pVV16 was found to be 16.57% in contrast to 26.14% in the Msmeg‐PPE18 group.…”

STAT5A Modulates Chemokine Receptor CCR6 Expression and Enhances Pre‐B Cell Growth in a CCL20‐Dependent Manner

“…CCR6+ B cells have recently been shown to enter inflamed skin in which CCL20 is expressed, suggesting a key role for local host defense mechanisms [Paradis et al, ]. In addition, CCR6 deficiency has been shown to cause reduced intestinal IgA responses to oral Ag [Xu et al, ] resulting from alterations in intestinal tissue formation owing to abnormal responses to microbial Ag [McDonald et al, ].…”