HMGB1 promotes CXCL12‐dependent egress of murine B cells from Peyer's patches in homeostasis

Abstract

High mobility group box‐1 protein (HMGB1) is an alarmin that, once released, promotes inflammatory responses, alone and as a complex with the chemokine CXCL12. Here, we report that the HMGB1–CXCL12 complex plays an essential role also in homeostasis by controlling the migration of B lymphocytes. We show that extracellular HMGB1 is critical for the CXCL12‐dependent egress of B cells from the Peyer's patches (PP). This promigratory function of the complex was restricted to the PPs, since HMGB1 was not required for B‐cell migratory processes in other locations. Accordingly, we detected higher constitutive levels of the HMGB1–CXCL12 complex in PPs than in other lymphoid organs. HMGB1–CXCL12 in vivo inhibition was associated with a reduced basal IgA production in the gut. Collectively, our results demonstrate a role for the HMGB1–CXCL12 complex in orchestrating B‐cell trafficking in homeostasis, and provide a novel target to control lymphocyte migration in mucosal immunity.

CXCR4/CXCL12 Activities in the Tumor Microenvironment and Implications for Tumor Immunotherapy

“…CXC chemokines are also classified as inflammatory, homeostatic, or dual function. CXCL12 is a homeostatic chemokine that can exist in monomeric and dimeric forms [18]; it has key roles in embryogenesis, angiogenesis, lymphopoiesis and regulates hematopoietic stem cell trafficking in physiological and pathological conditions [12,19,20].…”

Poly I:C elicits broader and stronger humoral and cellular responses to a Plasmodium vivax circumsporozoite protein malaria vaccine than Alhydrogel in mice

“…This may hinder the transmission of calcium ions within B cells, impacting the regulation of B-cell activation and differentiation (reviewed by 70 , 71 ). Additionally, the downregulation of Hmgb1-rs17 may contribute to the accumulation of splenic PCs and MBCs ( Figures 3 , 4 ) by inhibiting B-cell egress from lymphoid tissues, such as Peyer’s patches ( 72 ). The regulation of vaccine-derived responses by regulatory T cells (Tregs) could also be affected, as indicated by the downregulation of Gm10408 and Gm14391 ( Supplementary Table 1 ), potentially limiting their frequency or functionality in the spleens of Poly I:C-adjuvanted vaccinees ( Supplementary Table 1 ).…”

HMGB1-Mediated Activation of the Inflammatory-Reparative Response Following Myocardial Infarction

“…HMGB1 has been demonstrated to affect B cells activation in response to endogenous TLR9 ligands [ 103 ] and through TLR2 and CD36 in inflammatory bowel disease [ 104 ]. Moreover, a recent study has demonstrated that the HMGB1–CXCL12 complex influences B-cell trafficking in Peyer’s patches (PPs) and IgA production in the intestine [ 105 ], and, even if this role was observed in homeostatic condition, it is possible that HMGB1 may exert similar effects during acute or chronic inflammation. All these data may suggest a possible role of HMGB1 in the regulation of B cells during the inflammatory reparative response that has not been investigated yet.…”