1. Neutrophils, dendritic cells and macrophages deliver activation signals to marginal zone B cells.
Neutrophils, dendritic cells and macrophages deliver activation signals to marginal zone B cells. (1) Pre‐immune conditions. In humans, marginal zone B cells receive help from NBH cells, which probably arise from the reprogramming of conventional circulating neutrophils by cytokines—including IL‐10—released by splenic perifollicular sinusoidal endothelial cells and macrophages. This process is activated by the physiological translocation of small amounts of microbial products from mucosal surfaces, including TLR ligands. NBH cells trigger CSR, SHM and the formation of plasmablasts that secrete IgM, IgG or IgA by activating marginal zone B cells through BAFF, APRIL and IL‐21. Microbial products trapped by NET‐like projections emanating from NBH cells might enhance the activation of marginal zone B cells by engaging immunoglobulin receptors and TLRs. This pathway leads to the formation of a pre‐immune antibody repertoire to conserved microbial antigens. (2) Post‐immune conditions. Marginal zone B cells receive activation signals from dendritic cells (DCs) and macrophages that migrate to perifollicular areas of the spleen after capturing blood‐borne microbes. These DCs and macrophages not only release BAFF and APRIL, but also present native antigen, which activates immunoglobulin receptors and TLRs in marginal zone B cells. The resulting marginal zone reaction induces some CSR but no SHM (at least in mice) and generates short‐lived plasmablasts secreting IgM and IgG antibodies. APRIL, a proliferation‐inducing ligand; BAFF, B‐cell‐activating factor of the TNF family; CD40L, CD40 ligand; CSR, class switch recombination; CXCL13, CXC chemokine ligand 13; CXCR5, CXC chemokine receptor 5; FDC, folicullar dendritic cell; IgA/G/M, immunoglobulin A/G/M; IL, interleukin; NBH cell, B cell helper neutrophil; MHC, major histocompatibility complex; NET, neutrophil extracellular trap; SHM, somatic hypermutation; TCR, T‐cell receptor; TFH, T follicular helper cell.; TLR, Toll‐like receptor.
Andrea Cerutti et al. EMBO Rep. 2012;13:
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