Neutrophils Zone in to Help B Cells

RESEARCH HIGHLIGHTS

Nature Reviews Immunology | AOP, published online 20 January 2012; doi:10.1038/nri3159

ANTIBODY RESPONSES Neutrophils zone in to help B cells

Neutrophils are key effector cells of Remarkably, splenic neutrophils, IL‑10, which promoted B cell helper the innate immune system that are but not neutrophils isolated from the activity in circulating neutrophils. rapidly recruited to infected tissues to blood, promoted IgM secretion by Neutrophils also acquired B cell helper clear pathogens. Recently, researchers marginal zone B cells in vitro. The functions following migration across have shown that neutrophils also splenic neutrophils were as effective LPS-activated SECs. Interestingly, shape adaptive immune responses by as splenic CD4+ T cells in inducing marked colonization of the spleen by interacting with T cells and dendritic marginal zone B cell activation and neutrophils was found to occur early cells (DCs). In an exciting new study were more effective than either splenic after birth, at a time that coincided using human tissues, Andrea Cerutti macrophages or DCs. Interestingly, with bacterial colonization of mucosal and colleagues describe yet another splenic neutrophils inhibited the surfaces. Therefore, the authors mechanism by which neutrophils proliferation of activated CD4+ T cells, propose that commensal bacteria drive promote immunity to micro suggesting that these ‘helper’ neutro the development of helper neutrophils organisms: neutrophils colonize phils suppress T cells to promote T cell- that promote T cell-independent the marginal zone of the spleen and independent antibody production. antibody responses. support T cell-independent antibody More detailed studies showed that the Finally, by assessing patients with responses by activating marginal helper neutrophils induced upregu various neutrophil disorders, the zone B cells. lation of activation-induced cytidine authors provided evidence that helper The authors set out to explore deaminase (AID; also known as neutrophils support marginal zone whether neutrophils interact with AICDA) expression in marginal zone B cell responses in vivo. Compared B cells in human lymphoid organs B cells and promoted antibody class with healthy controls, patients with under homeostatic conditions. switching, somatic hypermutation neutrophil defects had normal Although few neutrophils were and plasma cell differentiation. numbers of total circulating B cells found in non-inflamed peripheral Compared with circulating neutro but fewer marginal zone B cells. lymph nodes, tonsils or Peyer’s phils, the helper neutrophils expressed Accordingly, although these patients patches, neutrophils could be higher levels of B cell stimulatory had normal levels of antibodies detected in the marginal zone in molecules, such as B cell-activating specific for T cell-dependent antigens, healthy human spleens. Splenic factor (BAFF), a proliferation- such as tetanus or diphtheria toxins, neutrophils extended projections inducing ligand (APRIL), CD40L they had decreased levels of antibodies that reached marginal zone B cells and interleukin‑21 (IL‑21), as well with specificity for T cell-independent and were also in close contact with as higher levels of the B cell chemo antigens, such as LPS, lipoteichoic acid sinusoidal endothelial cells (SECs), attractants CXC-chemokine ligand 12 and peptidoglycan. Taken together, macrophages and DCs in the (CXCL12) and CXCL13. Further these findings suggest that neutrophils marginal zone. A similar pattern of experiments involving blockade interact with marginal zone B cells neutrophil localization was observed of BAFF, APRIL or IL‑21 showed to support innate-like antibody in healthy macaques, but not in that these factors are important for responses that may be important for diseased human spleens, in which neutrophil helper functions. protection against systemic infections. neutrophils extensively infiltrated Notably, the splenic environment Yvonne Bordon follicular regions. Therefore, under itself supported the development of ORIGINAL RESEARCH PAPER Puga, I. et al. homeostatic conditions, neutrophils helper neutrophils. In response to B cell-helper neutrophils stimulate the colonize the marginal zone, but not lipopolysaccharide (LPS) and other diversification and production of immunoglobulin the follicles, of the spleen. But what conserved microbial products, splenic in the marginal zone of the spleen. Nature Immunol. 25 Dec 2011 (doi: 10.1038/ni.2194) is their function there? macrophages and SECs produced